Comparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.

ABSTRACT: Administration of AAV-based gene therapies into the intra-cerebrospinal fluid (CSF) compartments via routes such as lumbar puncture (LP) has been implemented as an alternative to intravenous dosing to target the CNS regions. This route enables lower doses, decreases systemic toxicity, and circumvents intravascular pre-existing anti-AAV antibodies. In this study, AAV9-GFP vectors were administered via LP to juvenile cynomolgus macaques with and without pre-existing serum anti-AAV9 antibodies at a 5.0 × 10¹³ vector genomes per mL (vg/mL) dose and examined for 28 days. CNS and peripheral tissues were surveyed for vector genome, mRNA, and protein expression. Histopathology, clinical pathology, and humoral immune response to the viral capsid and transgene were also assessed. In addit

SUBMITTER: Guibinga GH 

PROVIDER: S-EPMC11664412 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature