Microglia-specific transduction via AAV11 armed with IBA1 promoter and miRNA-9 targeting sequences
Luo, N.; Lin, K.; Cai, Y.; Sui, X.; Zhang, Z.; Xing, J.; Liu, G.; Yuan, W.; Wang, J.; Xu, F.
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Microglia, as resident immune cells in the central nervous system (CNS), are closely related to human health and the pathogenesis of various CNS diseases, making them compelling targets for therapeutic interventions. However, functional and therapeutic studies of microglia remain significant challenges largely due to the lack of tools capable of efficiently and specifically transducing microglia. Herein, we evaluated the specificity and efficiency of various adeno-associated virus (AAV) vectors armed with the mIBA1 promoter and miRNA-9 targeting sequences in transducing microglia within the caudate putamen (CPu) brain region, and found that AAV11 mediates more specific and efficient transduction of microglia. Subsequently, we further demonstrated that AAV11 also exhibits high transduction specificity for microglia across various brain areas and within the spinal cord. Finally, by reducing the injection dosage, we employed AAV11 for sparse labeling of microglia. This work provides a promising tool for advancing both the functional investigation and therapeutic targeting of microglia.
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