Publications<\/h1><\/div><\/div><\/div>Insight into our projects and continued progress<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Highlighted publications<\/h2><\/div><\/div><\/div>A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene<\/a><\/h3>\nHere, we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice.<\/p>\n
We modulated expression of Lama1 in a mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter.<\/p>\n
Our data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.<\/p>\n<\/div><\/div><\/div>
![\"Figure](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/final.png\")
<\/a><\/span><\/div><\/div><\/div><\/div>Saturation variant interpretation using CRISPR prime editing<\/a><\/h3>\nHere, we adapted CRISPR prime editing for high-throughput variant classification and combined it with a strategy that allows for haploidization of any locus, which simplifies variant interpretation.<\/p>\n
We demonstrate the utility of saturation prime editing (SPE) by applying it to the NPC intracellular cholesterol transporter 1 gene (NPC1), mutations in which cause the lysosomal storage disorder Niemann\u2013Pick disease type C.<\/p>\n
In sum, we show that SPE allows for efficient, accurate functional characterization of genetic variants<\/p>\n<\/div><\/div><\/div>
![\"Figure](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/fig1.png\")
<\/a><\/span><\/div><\/div><\/div><\/div>Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism<\/a><\/h3>\nHere, we correct a splice-site mutation that causes the exclusion of exon 2 from Lama2 mRNA and the truncation of Lama2 protein in a mouse model of MDC1A.<\/p>\n
Through systemic delivery of adeno-associated virus (AAV) carrying clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing components, we simultaneously excise an intronic region containing the mutation and create a functional donor splice site through NHEJ.<\/p>\n
This strategy leads to the inclusion of exon 2 in the Lama2 transcript and restoration of full-length Lama2 protein. Results also displayed substantial improvement in muscle histopathology and function without signs of paralysis.<\/p>\n<\/div><\/div><\/div>
![\"Figure](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/fig-2.png\")
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Insight into our projects and continued progress<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Highlighted publications<\/h2><\/div><\/div><\/div>A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene<\/a><\/h3>\nHere, we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice.<\/p>\n
We modulated expression of Lama1 in a mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter.<\/p>\n
Our data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Saturation variant interpretation using CRISPR prime editing<\/a><\/h3>\nHere, we adapted CRISPR prime editing for high-throughput variant classification and combined it with a strategy that allows for haploidization of any locus, which simplifies variant interpretation.<\/p>\n
We demonstrate the utility of saturation prime editing (SPE) by applying it to the NPC intracellular cholesterol transporter 1 gene (NPC1), mutations in which cause the lysosomal storage disorder Niemann\u2013Pick disease type C.<\/p>\n
In sum, we show that SPE allows for efficient, accurate functional characterization of genetic variants<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism<\/a><\/h3>\nHere, we correct a splice-site mutation that causes the exclusion of exon 2 from Lama2 mRNA and the truncation of Lama2 protein in a mouse model of MDC1A.<\/p>\n
Through systemic delivery of adeno-associated virus (AAV) carrying clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing components, we simultaneously excise an intronic region containing the mutation and create a functional donor splice site through NHEJ.<\/p>\n
This strategy leads to the inclusion of exon 2 in the Lama2 transcript and restoration of full-length Lama2 protein. Results also displayed substantial improvement in muscle histopathology and function without signs of paralysis.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene<\/a><\/h3>\nHere, we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice.<\/p>\n
We modulated expression of Lama1 in a mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter.<\/p>\n
Our data demonstrated the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Saturation variant interpretation using CRISPR prime editing<\/a><\/h3>\nHere, we adapted CRISPR prime editing for high-throughput variant classification and combined it with a strategy that allows for haploidization of any locus, which simplifies variant interpretation.<\/p>\n
We demonstrate the utility of saturation prime editing (SPE) by applying it to the NPC intracellular cholesterol transporter 1 gene (NPC1), mutations in which cause the lysosomal storage disorder Niemann\u2013Pick disease type C.<\/p>\n
In sum, we show that SPE allows for efficient, accurate functional characterization of genetic variants<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism<\/a><\/h3>\nHere, we correct a splice-site mutation that causes the exclusion of exon 2 from Lama2 mRNA and the truncation of Lama2 protein in a mouse model of MDC1A.<\/p>\n
Through systemic delivery of adeno-associated virus (AAV) carrying clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing components, we simultaneously excise an intronic region containing the mutation and create a functional donor splice site through NHEJ.<\/p>\n
This strategy leads to the inclusion of exon 2 in the Lama2 transcript and restoration of full-length Lama2 protein. Results also displayed substantial improvement in muscle histopathology and function without signs of paralysis.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Saturation variant interpretation using CRISPR prime editing<\/a><\/h3>\nHere, we adapted CRISPR prime editing for high-throughput variant classification and combined it with a strategy that allows for haploidization of any locus, which simplifies variant interpretation.<\/p>\n
We demonstrate the utility of saturation prime editing (SPE) by applying it to the NPC intracellular cholesterol transporter 1 gene (NPC1), mutations in which cause the lysosomal storage disorder Niemann\u2013Pick disease type C.<\/p>\n
In sum, we show that SPE allows for efficient, accurate functional characterization of genetic variants<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism<\/a><\/h3>\nHere, we correct a splice-site mutation that causes the exclusion of exon 2 from Lama2 mRNA and the truncation of Lama2 protein in a mouse model of MDC1A.<\/p>\n
Through systemic delivery of adeno-associated virus (AAV) carrying clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing components, we simultaneously excise an intronic region containing the mutation and create a functional donor splice site through NHEJ.<\/p>\n
This strategy leads to the inclusion of exon 2 in the Lama2 transcript and restoration of full-length Lama2 protein. Results also displayed substantial improvement in muscle histopathology and function without signs of paralysis.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div>Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism<\/a><\/h3>\nHere, we correct a splice-site mutation that causes the exclusion of exon 2 from Lama2 mRNA and the truncation of Lama2 protein in a mouse model of MDC1A.<\/p>\n
Through systemic delivery of adeno-associated virus (AAV) carrying clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing components, we simultaneously excise an intronic region containing the mutation and create a functional donor splice site through NHEJ.<\/p>\n
This strategy leads to the inclusion of exon 2 in the Lama2 transcript and restoration of full-length Lama2 protein. Results also displayed substantial improvement in muscle histopathology and function without signs of paralysis.<\/p>\n<\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
<\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div><\/div><\/div>All publications<\/h2><\/div>View all of our recent publications listed chronologically<\/p>\n<\/div>
<\/div><\/div>2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
View all of our recent publications listed chronologically<\/p>\n<\/div>
2025<\/h3>\n<\/div>Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Mollica A, Omer S, Forguson G, Steiman S, Evagelou SL, Naumenko S, Walker S, Li LY, Teeling A, Lindsay K, Erwood S. Mutations in the \u03b2-tubulin TUBB impair ciliogenesis and are associated with ciliopathy-like phenotypes. Nature Communications. 2025 Nov 27;16(1):10637.<\/p>\n<\/div>
Hung, J. E., Brewer, R. A., Elbakr, L., Mollica, A., Forguson, G., Chan, W. S., & Ivakine, E. A. (2024). Precise template-free correction restores gene function in Tay-Sachs disease while reframing is ineffective. Molecular Therapy-Nucleic Acids, 36(1).<\/p>\n<\/div>
2024<\/h3>\n<\/div>Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div>2023<\/h3>\n<\/div>Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div>Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div>2022<\/h3>\n<\/div>Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div>Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div>Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div>Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div>2021<\/h3>\n<\/div>Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div>Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div>Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div>2020<\/h3>\n<\/div>Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div>Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div>2019<\/h3>\n<\/div>Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div>Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div>Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div>Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div>2018<\/h3>\n<\/div>Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div>2017<\/h3>\n<\/div>Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Rizvi, S. Z., Chan, W. S., Maino, E., Steiman, S., Forguson, G., Klepfish, M., … & Ivakine, E. A. (2024). Multi-gene duplication removal in an engineered human cellular MECP2 duplication syndrome model with an IRAK1-MECP2 duplication. Molecular Therapy-Nucleic Acids, 35(4) e102356.<\/p>\n<\/div>
Maino E, Scott O, Rizvi SZ, Chan WS, Visuvanathan S, Zablah YB, Li H, Sengar AS, Salter MW, Jia Z, Rossant J, Cohn RD, Gu B, Ivakine EA. (2024). A Cas9-fusion proximity-based approach generates an Irak1-Mecp2 tandem duplication mouse model for the study of MeCP2 duplication syndrome<\/a>. Disease Models & Mechanisms, Epub ahead of print PMID 38881329.<\/p>\n<\/div> Scott, O., Visuvanathan, S., Reddy, E., Mahamed, D., Gu, B., Roifman, C. M., Cohn, R. D., Guidos, C. J., & Ivakine, E. A<\/b>. (2023). The human Stat1 gain-of-function T385M mutation causes expansion of activated T-follicular helper\/T-helper 1-like CD4 T cells and sex-biased autoimmunity in specific pathogen-free mice.<\/a> Frontiers in immunology, 14, 1183273.<\/p>\n<\/div> Tillotson, R., Yan, K., Ruston, J., de Young, T., C\u00f3rdova, A., Turcotte-Cardin, V., Yee, Y., Taylor, C., Visuvanathan, S., Babbs, C., Ivakine, E. A<\/b>., Sled, J. G., Nieman, B. J., Picketts, D. J., & Justice, M. J. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects.<\/a> Human molecular genetics<\/i>, ddad075. Advance online publication.<\/p>\n<\/div> Schultz, M. L., Schache, K. J., Azaria, R. D., Kuiper, E. Q., Erwood, S., Ivakine, E. A<\/b>., Farhat, N. Y., Porter, F. D., Pathmasiri, K. C., Cologna, S. M., Uhler, M. D., & Lieberman, A. P. (2022). Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease<\/a>. JCI insight<\/i>, 7<\/i>(23), e160308.<\/p>\n<\/div> Teng, A. C. T., Tavassoli, M., Shrestha, S., Marks, R. M., McFadden, M. J., Evagelou, S. L., Lindsay, K., Vandenbelt, A., Li, W., Ivakine, E.<\/b>, Cohn, R., Santerre, J. P., & Gramolini, A. O. (2022). An efficient and cost-effective purification protocol for Staphylococcus aureus Cas9 nuclease. <\/a>STAR protocols<\/i>, 4<\/i>(1), 101933. Advance online publication.<\/p>\n<\/div> Fatehi, S., Marks, R. M., Rok, M. J., Perillat, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2023). Advances in CRISPR\/Cas9 Genome Editing for the Treatment of Muscular Dystrophies.<\/a> Human gene therapy<\/i>, 34<\/i>(9-10), 388\u2013403.<\/p>\n<\/div> Erwood, S., Bily, T. M. I., Lequyer, J., Yan, J., Gulati, N., Brewer, R. A., Zhou, L., Pelletier, L., Ivakine, E. A<\/b>., & Cohn, R. D. (2022). Saturation variant interpretation using CRISPR prime editing.<\/a> Nature biotechnology<\/i>, 40<\/i>(6), 885\u2013895.<\/p>\n<\/div> Maino, E., Wojtal, D., Evagelou, S. L., Farheen, A., Wong, T. W. Y., Lindsay, K., Scott, O., Rizvi, S. Z., Hyatt, E., Rok, M., Visuvanathan, S., Chiodo, A., Schneeweiss, M., Ivakine, E. A<\/b>., & Cohn, R. D. (2021). Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression<\/a>. EMBO molecular medicine<\/i>, 13<\/i>(5), e13228.<\/p>\n<\/div> Scott, O., Lindsay, K., Erwood, S., Mollica, A., Roifman, C. M., Cohn, R. D., & Ivakine, E. A.<\/b> (2021). STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.<\/a> NPJ genomic medicine<\/i>, 6<\/i>(1), 34.<\/p>\n<\/div> Shrestha, S., McFadden, M. J., Teng, A. C. T., Chang, P. D. M., Deng, J., Wong, T. W. Y., Cohn, R. D., Ivakine, E. A<\/b>., Gramolini, A. O., & Santerre, J. P. (2021). Self-Assembled Oligo-Urethane Nanoparticles: Their Characterization and Use for the Delivery of Active Biomolecules into Mammalian Cells.<\/a> ACS applied materials & interfaces<\/i>, 13<\/i>(49), 58352\u201358368.<\/p>\n<\/div> Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A<\/b>. (2020). Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.<\/a> Molecular therapy. Methods & clinical development<\/i>, 17<\/i>, 1118\u20131128.<\/p>\n<\/div> Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olgu\u00edn, P., Ivakine, E. A<\/b>., & Cohn, R. D. (2020). A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd<\/i> deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy.<\/a> Disease models & mechanisms<\/i>, 13<\/i>(9), dmm045369.<\/p>\n<\/div> Kemaladewi, D. U., Bassi, P. S., Erwood, S., Al-Basha, D., Gawlik, K. I., Lindsay, K., Hyatt, E., Kember, R., Place, K. M., Marks, R. M., Durbeej, M., Prescott, S. A., Ivakine, E. A.<\/b>, & Cohn, R. D. (2019). A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. <\/a>Nature<\/i>, 572<\/i>(7767), 125\u2013130.<\/p>\n<\/div> Laselva, O., Erwood, S., Du, K., Ivakine, Z<\/b>., & Bear, C. E. (2019). Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.<\/a> FASEB bioAdvances<\/i>, 1<\/i>(10), 661\u2013670.<\/p>\n<\/div> Mennesson, M., Rydgren, E., Lipina, T., Sokolowska, E., Kulesskaya, N., Morello, F., Ivakine, E<\/b>., Voikar, V., Risbrough, V., Partanen, J., & Hovatta, I. (2019). Kainate receptor auxiliary subunit NETO2 is required for normal fear expression and extinction.<\/a> Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology<\/i>, 44<\/i>(11), 1855\u20131866.<\/p>\n<\/div> Erwood, S., Brewer, R. A., Bily, T. M. I., Maino, E., Zhou, L., Cohn, R. D., & Ivakine, E. A. <\/b>(2019). Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.<\/a> Genome research<\/i>, 29<\/i>(12), 2010\u20132019.<\/p>\n<\/div> Kemaladewi, D. U., Benjamin, J. S., Hyatt, E., Ivakine, E. A<\/b>., & Cohn, R. D. (2018). Increased polyamines as protective disease modifiers in congenital muscular dystrophy. <\/a>Human molecular genetics<\/i>, 27<\/i>(11), 1905\u20131912.<\/p>\n<\/div> Kemaladewi, D. U., Maino, E., Hyatt, E., Hou, H., Ding, M., Place, K. M., Zhu, X., Bassi, P., Baghestani, Z., Deshwar, A. G., Merico, D., Xiong, H. Y., Frey, B. J., Wilson, M. D., Ivakine, E. A<\/b>., & Cohn, R. D. (2017). Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism.<\/a> Nature medicine<\/i>, 23<\/i>(8), 984\u2013989.<\/p>\n<\/div><\/div><\/div><\/div><\/div>2023<\/h3>\n<\/div>
2022<\/h3>\n<\/div>
2021<\/h3>\n<\/div>
2020<\/h3>\n<\/div>
2019<\/h3>\n<\/div>
2018<\/h3>\n<\/div>
2017<\/h3>\n<\/div>