Journal article
C. M. Suriano, Jessica L. Verpeut, Neerav Kumar, Jie Ma, C. Jung, L. Boulanger
bioRxiv, 2021
bioRxiv, 2021
Semantic Scholar
DOI
Cite
Cite
APA
Click to copy
Suriano, C. M., Verpeut, J. L., Kumar, N., Ma, J., Jung, C., & Boulanger, L. (2021). Adeno-associated virus (AAV) reduces cortical dendritic complexity in a TLR9-dependent manner. BioRxiv.
Chicago/Turabian
Click to copy
Suriano, C. M., Jessica L. Verpeut, Neerav Kumar, Jie Ma, C. Jung, and L. Boulanger. “Adeno-Associated Virus (AAV) Reduces Cortical Dendritic Complexity in a TLR9-Dependent Manner.” bioRxiv (2021).
MLA
Click to copy
Suriano, C. M., et al. “Adeno-Associated Virus (AAV) Reduces Cortical Dendritic Complexity in a TLR9-Dependent Manner.” BioRxiv, 2021.
BibTeX Click to copy
@article{c2021a,
title = {Adeno-associated virus (AAV) reduces cortical dendritic complexity in a TLR9-dependent manner},
year = {2021},
journal = {bioRxiv},
author = {Suriano, C. M. and Verpeut, Jessica L. and Kumar, Neerav and Ma, Jie and Jung, C. and Boulanger, L.}
}
Abstract
Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery in the nervous system. AAVs are widely used in research and are the basis of multiple FDA-approved gene therapies. Here, we find that the immune response to AAV’s genome reduces dendritic complexity in mammalian cortex. Dendritic loss associated with AAV-mediated gene delivery occurs at experimentally-relevant titers, cannot be explained by responses to transgene expression or surgery, and is not restricted to a particular capsid serotype, encoded transgene, promoter, or production facility. AAV-associated dendritic loss is accompanied by a decrease in the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and upregulation of immune molecules that can limit dendritic complexity and synaptic transmission. Blocking detection of unmethylated CpG-rich DNA via Toll-like receptor 9 (TLR9) protects dendritic complexity, suggesting that immunodetection of a core feature of the AAV genome triggers dendritic loss. These results reveal previously unsuspected impacts of AAV on neuronal structure and function and identify TLR9 inhibitors as important tools to improve the safety and efficacy of AAV-mediated gene delivery in the nervous system.