Genome-scale CRISPR screen to identify cellular restriction factors that inhibit transgene expression from adeno-associated virus vectors

Adeno-associated virus (AAV) vectors are one of the leading platforms for gene delivery for the treatment of human genetic diseases, but the antiviral cellular mechanisms that interfere with optimal transgene expression are incompletely understood. Here, we performed two genome-scale CRISPR screens using CRISPR KO in A549 human alveolar basal epithelial cells and CRISPRi in K562 myeloid lymphoblast cells to identify cellular factors that restrict transgene expression from AAV vectors.