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bioRxiv · 10.1101/2023.12.12.571321

Simple and Highly Specific Targeting of Resident Microglia with Adeno-Associated Virus

Serrano, C.·Cananzi, S.·Shen, T.·Wang, L.-L.·Zhang, C.-L.
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Abstract

Microglia, as the immune cells of the central nervous system (CNS), play dynamic roles in both health and diseased conditions. The ability to genetically target microglia using viruses is crucial for understanding their functions and advancing microglia-based treatments. We here show that resident microglia can be simply and specifically targeted using adeno-associated virus (AAV) vectors containing a 466-bp DNA fragment from the human IBA1 (hIBA1) promoter. This targeting approach is applicable to both resting and reactive microglia. When combining the short hIBA1 promoter with the target sequence of miR124, up to 95% of transduced cells are identified as microglia. Such a simple and highly specific microglia-targeting strategy may be further optimized for research and therapeutics. Significance StatementBrain microglia play critical roles in human health and diseases. Genetic manipulation of these cells will offer numerous therapeutic opportunities. However, there is a lack of relevant strategies to target these cells with high specificity since they are traditionally considered to be refractory to virus transduction. Through in vivo screening of many promoters, this study identified a short promoter from the human IBA1 gene. When incorporated into lentivirus or adeno-associated virus vectors, this promoter proves effective in driving gene expression with high specificity for brain microglia. Such a simple strategy will facilitate specific approaches for microglia-based research.

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Serrano, C., Cananzi, S., Shen, T., Wang, L.-L., Zhang, C.-L.. 2023-12-13. Simple and Highly Specific Targeting of Resident Microglia with Adeno-Associated Virus. https://doi.org/10.1101/2023.12.12.571321

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