AAV-mediated gene transfer is a promising platform still plagued by potential host-derived, antagonistic immune responses to therapeutic components. CpG-mediated TLR9 stimulation activates innate immune cells and leads to cognate T cell activation and suppression of transgene expression. Here, we demonstrate that CpG depletion increased expression of an antibody transgene product by 2-3-fold as early as 24 h post-vector administration in mice. No significant differences were noted in anti-transgene product/ anti-AAV capsid antibody production or cytotoxic gene induction. Instead, CpG depletion significantly reduced the presence of a pDC-like myeloid cell population, which was able to directly bind the antibody transgene product via Fc-FcγR interactions. Thus, we extend the mechanisms of TLR9-mediated antagonism of transgene expression in AAV gene therapy to include the actions of a previously unreported pDC-like cell population.
Keyphrases
- gene therapy
- dendritic cells
- immune response
- poor prognosis
- dna methylation
- toll like receptor
- regulatory t cells
- single cell
- inflammatory response
- cell therapy
- binding protein
- long non coding rna
- gene expression
- high throughput
- oxidative stress
- nuclear factor
- skeletal muscle
- metabolic syndrome
- high fat diet induced
- transcription factor
- heat stress