Investigating immune responses to the scaav9-hexm gene therapy treatment in tay–sachs disease and sandhoff disease mouse models

Shalini Kot, Subha Karumuthil-Melethil, Evan Woodley, Violeta Zaric, Patrick Thompson, Zhilin Chen, Erik Lykken, John G. Keimel, William F. Kaemmerer, Steven J. Gray, Jagdeep S. Walia

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


GM2 gangliosidosis disorders are a group of neurodegenerative diseases that result from a functional deficiency of the enzyme β-hexosaminidase A (HexA). HexA consists of an α-and β-subunit; a deficiency in either subunit results in Tay–Sachs 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 “non-self”-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 “non-self” proteins, and potentially improve treatment efficacy.

Original languageEnglish (US)
Article number6751
JournalInternational journal of molecular sciences
Issue number13
StatePublished - Jul 1 2021


  • Capsid
  • GM2
  • Gangliosidosis
  • HexM
  • Immunocompetence
  • Murine
  • Sandhoff
  • Tay-Sachs
  • Transgene

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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