时间: 10:00-12:00 on Fri., April. 8, 2022
题目: Engineered AAV Capsid Variants for Potent Gene Delivery to Microglia
As the resident immune cells in the central nervous system (CNS), microglia orchestrate CNS immune responses and dynamically sculpt neural circuits. Microglial dysfunction and mutations of microglia-specific genes have been implicated in many CNS diseases. Compared with other cell types in the brain (e.g., neurons and astrocytes), microglia are notoriously difficult to transduce using existing viral vectors. The study of microglia biology and the development of microglia-based gene therapies are in urgent need of efficient and safe vehicles for microglia transgene delivery. In this talk, I will discuss our recent work on developing adeno-associated virus (AAV) variants for microglia. Via directed evolution of the AAV capsid protein, we identified a set of AAV variants that mediate efficient in vitro and in vivo microglial transduction. The newly discovered AAV-cMG and AAV-MG variants are capable of delivering various genetic payloads into microglia with high efficiency, and enable sufficient transgene expression to support fluorescent labeling, Ca2+ and neurotransmitter imaging, and genome editing in microglia in vivo. Further, single-cell RNA sequencing showed that the AAV-MG variants mediate safe in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the applications of various genetically-encoded sensors and effectors in studying microglia-related biology and therapeutic interventions.