Effect of CpG Depletion of Vector Genome on CD8⁺ T Cell Responses in AAV Gene Therapy.

ABSTRACT: Adeno associated viral (AAV) vectors have emerged as a preferred platform for in vivo gene replacement therapy and represent one of the most promising strategies to treat monogenetic disorders such as hemophilia. However, immune responses to gene transfer have hampered human gene therapy in clinical trials. Over the past decade, it has become clear that innate immune recognition provides signals for the induction of antigen-specific responses against vector or transgene product. In particular, TLR9 recognition of the vector's DNA genome in plasmacytoid dendritic cells (pDCs) has been identified as a key factor. Data from clinical trials and pre-clinical studies implement CpG motifs in the vector genome as drivers of immune responses, especially of CD8⁺ T cell activation.

SUBMITTER: Bertolini TB 

PROVIDER: S-EPMC8200677 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature