The presence of CpGs in AAV gene therapy vectors induces a plasmacytoid dendritic cell-like population very early after administration.
Cell Immunol
; 399-400: 104823, 2024.
Article
in En
| MEDLINE
| ID: mdl-38520831
ABSTRACT
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Dendritic Cells
/
Genetic Therapy
/
Dependovirus
/
Transgenes
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Toll-Like Receptor 9
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Genetic Vectors
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Year:
2024
Type:
Article