Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment.

ABSTRACT: Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells' heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four

SUBMITTER: Maes ME 

PROVIDER: S-EPMC8516996 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature