{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:19:23Z","timestamp":1773868763125,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New Hope Research Foundation","award":["2013-010"],"award-info":[{"award-number":["2013-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>GM2 gangliosidosis disorders are a group of neurodegenerative diseases that result from a functional deficiency of the enzyme \u03b2-hexosaminidase A (HexA). HexA consists of an \u03b1- and \u03b2-subunit; a deficiency in either subunit results in Tay\u2013Sachs Disease (TSD) or Sandhoff Disease (SD), respectively. Viral vector gene transfer is viewed as a potential method of treating these diseases. A recently constructed isoenzyme to HexA, called HexM, has the ability to effectively catabolize GM2 gangliosides in vivo. Previous gene transfer studies have revealed that the scAAV9-HEXM treatment can improve survival in the murine SD model. However, it is speculated that this treatment could elicit an immune response to the carrier capsid and \u201cnon-self\u201d-expressed transgene. This study was designed to assess the immunocompetence of TSD and SD mice, and test the immune response to the scAAV9-HEXM gene transfer. HexM vector-treated mice developed a significant anti-HexM T cell response and antibody response. This study confirms that TSD and SD mouse models are immunocompetent, and that gene transfer expression can create an immune response in these mice. These mouse models could be utilized for investigating methods of mitigating immune responses to gene transfer-expressed \u201cnon-self\u201d proteins, and potentially improve treatment efficacy.<\/jats:p>","DOI":"10.3390\/ijms22136751","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T11:28:41Z","timestamp":1624447721000},"page":"6751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Investigating Immune Responses to the scAAV9-HEXM Gene Therapy Treatment in Tay\u2013Sachs Disease and Sandhoff Disease Mouse Models"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-0734","authenticated-orcid":false,"given":"Shalini","family":"Kot","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subha","family":"Karumuthil-Melethil","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Woodley","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Zaric","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Thompson","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pediatrics, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Lykken","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Keimel","sequence":"additional","affiliation":[{"name":"New Hope Research Foundation, North Oaks, MN 55127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F.","family":"Kaemmerer","sequence":"additional","affiliation":[{"name":"New Hope Research Foundation, North Oaks, MN 55127, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-8621","authenticated-orcid":false,"given":"Steven J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagdeep S.","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"},{"name":"Medical Genetics, Department of Pediatrics, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","first-page":"278","article-title":"Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs","volume":"3","author":"Sandhoff","year":"1968","journal-title":"Pathol. 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