{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:19:13Z","timestamp":1793942353463,"version":"4.8.0"},"reference-count":24,"publisher":"SAGE Publications","issue":"5-6","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>\n                    Epigenome editing technology holds great promise for treating diverse genetic disorders. In this study, we demonstrate epigenetic activation of the\n                    <jats:italic toggle=\"yes\">LAMA1<\/jats:italic>\n                    gene for the treatment of\n                    <jats:italic toggle=\"yes\">LAMA2<\/jats:italic>\n                    -CMD, a severe congenital muscle dystrophy (CMD) caused by biallelic mutations in the\n                    <jats:italic toggle=\"yes\">LAMA2<\/jats:italic>\n                    gene.\n                    <jats:italic toggle=\"yes\">LAMA1<\/jats:italic>\n                    is a sister homolog that is known to compensate for the function of\n                    <jats:italic toggle=\"yes\">LAMA2<\/jats:italic>\n                    . However, supplementing\n                    <jats:italic toggle=\"yes\">LAMA1<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">LAMA2<\/jats:italic>\n                    gene via viral platform is not feasible due to the large size of their coding sequences. Through a single administration of our adeno-associated virus (AAV) vector encoding all the necessary elements for epigenetic activation, we observed significant\n                    <jats:italic toggle=\"yes\">LAMA1<\/jats:italic>\n                    gene upregulation and phenotype improvements in mouse disease models. The muscle-tropic AAV capsid exhibited desired vector biodistribution and promising pharmacodynamics with good safety profiles in 2-year-old juvenile nonhuman primates (NHPs). Moreover, administration to 8-month-old infant NHPs demonstrated superior pharmacodynamics compared with 2-year-old juveniles, even at half the dose. Our approach holds broad applicability for a range of loss-of-function genetic disorders and could offer a therapeutic breakthrough where active epigenome offers clinical benefit.\n                  <\/jats:p>","DOI":"10.1177\/10430342251401873","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T10:04:21Z","timestamp":1766570661000},"page":"210-222","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficient LAMA1 Gene Activation by Epigenome Editing as a Therapeutic Approach for LAMA2-CMD"],"prefix":"10.1177","volume":"37","author":[{"given":"Yuanbo","family":"Qin","sequence":"first","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Akbulut","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajakumar","family":"Mandraju","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Connolly","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bechill","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Assadian","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Foster","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Shottek","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Levy","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Benoit","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Yamagata","sequence":"additional","affiliation":[{"name":"Modalis Therapeutics, Inc., Waltham, Massachusetts, 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