All current market-approved gene therapy medical products for in vivo gene therapy of monogenic diseases rely on adeno-associated virus (AAV) vectors. Advances in gene editing technologies and vector engineering have expanded the spectrum of target cells and, thus, diseases that can be addressed. Consequently, AAV vectors are now being explored to modify cells of the hematopoietic system, including hematopoietic stem and progenitor cells (HSPCs), to develop novel strategies to treat monogenic diseases, but also to generate cell- and vaccine-based immunotherapies. However, the cell types that represent important new targets for the AAV vector system are centrally involved in immune responses against the vector and its transgene product as discussed briefly in the first part of this review. In the second part, studies exploring AAV vectors for genetic engineering of HSPCs, T and B lymphocytes, and beyond are presented.
Keywords: adeno-associated virus (AAV) vectors; gene editing; gene therapy; immunotherapy; innate immune responses.