A blood-brain barrier-penetrant AAV gene therapy improves neurological function in symptomatic mucolipidosis IV mice.

ABSTRACT: Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using adeno-associated vector 9 (AAV9) and AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying disease course in a mouse model of MLIV by the human MCOLN1 gene transfer. Here, using a primate-enabling capsid AAV.CPP.16 (CPP16), we constructed a new, clinic-oriented MCOLN1 gene expression vector and demonstrated its efficacy in the preclinical model of MLIV. Systemic administration of CPP16-MCOLN1 in adult symptomatic Mcoln1 ^-/- mice at a dose of 1e12 vg per mouse resulted in MCOLN1 expression in the brain and peripheral tissues, alleviated brain pathol

SUBMITTER: Sangster ML 

PROVIDER: S-EPMC11201152 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature