Identification of Novel Retinal Pericyte-Targeting rAAV Vectors Through Directed Evolution.

ABSTRACT:

Purpose

Retinal pericytes play a vital role in maintaining retinal homeostasis, and their dysfunction underlies pathogenesis in such vascular eye diseases as diabetic retinopathy and wet age-related macular degeneration. Consequently, retinal pericytes are attractive therapeutic targets for gene therapy, but effectively targeting pericytes with recombinant adeno-associated virus (rAAV) vectors remains a challenge.

Methods

We introduced genetic modifications into the surface-exposed variable regions of the rAAV2/2 capsid to generate a complex library (>1 × 107) of capsid mutants that were then screened for preferential tropism toward retinal pericytes. Using the Tg(Cspg4-DsRed.T1)1Akik/J reporter mouse model, which has red fluorescent pericytes that can be isolated via flow c

SUBMITTER: Patel DD 

PROVIDER: S-EPMC9428359 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature