TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy
SN Ashley, S Somanathan, AR Giles, JM Wilson - Cellular immunology, 2019 - Elsevier
An ongoing concern of in vivo gene therapy is adaptive immune responses against the
protein product of a transgene, particularly for recessive diseases in which antigens are not
presented to lymphocytes during central tolerance induction. Here we show that Toll-like
receptor 9 (TLR9) signaling activates T cells against an epitope tagged mitochondria-
targeted ornithine transcarbamylase (OTC) following the administration of a systemic adeno-
associated virus (AAV) vector. Using a transgenic mouse model system, we demonstrate …
protein product of a transgene, particularly for recessive diseases in which antigens are not
presented to lymphocytes during central tolerance induction. Here we show that Toll-like
receptor 9 (TLR9) signaling activates T cells against an epitope tagged mitochondria-
targeted ornithine transcarbamylase (OTC) following the administration of a systemic adeno-
associated virus (AAV) vector. Using a transgenic mouse model system, we demonstrate …