| First Author | Lin R | Year | 2022 |
| Journal | Nat Methods | Volume | 19 |
| Issue | 8 | Pages | 976-985 |
| PubMed ID | 35879607 | Mgi Jnum | J:372939 |
| Mgi Id | MGI:8250638 | Doi | 10.1038/s41592-022-01547-7 |
| Citation | Lin R, et al. (2022) Directed evolution of adeno-associated virus for efficient gene delivery to microglia. Nat Methods 19(8):976-985 |
| abstractText | As the resident immune cells in the central nervous system (CNS), microglia orchestrate immune responses and dynamically sculpt neural circuits in the CNS. Microglial dysfunction and mutations of microglia-specific genes have been implicated in many diseases of the CNS. Developing effective and safe vehicles for transgene delivery into microglia will facilitate the studies of microglia biology and microglia-associated disease mechanisms. Here, we report the discovery of adeno-associated virus (AAV) variants that mediate efficient in vitro and in vivo microglial transduction via directed evolution of the AAV capsid protein. These 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, Ca(2+) and neurotransmitter imaging and genome editing in microglia in vivo. Furthermore, single-cell RNA sequencing shows that the AAV-MG variants mediate in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the use of various genetically encoded sensors and effectors in the study of microglia-related biology. |
