Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.

ABSTRACT: Adeno-associated virus (AAV)-based gene therapy has enjoyed great successes over the past decade, with Food and Drug Administration-approved therapeutics and a robust clinical pipeline. Nonetheless, barriers to successful translation remain. For example, advanced age is associated with impaired brain transduction, with the diminution of infectivity depending on anatomical region and capsid. Given that CNS gene transfer is often associated with neurodegenerative diseases where age is the chief risk factor, we sought to better understand the causes of this impediment. We assessed two AAV variants hypothesized to overcome factors negatively impacting transduction in the aged brain; specifically, changes in extracellular and cell-surface glycans, and intracellular transport. We evaluated a hep

SUBMITTER: Sandoval IM 

PROVIDER: S-EPMC11497394 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature