Microglia targeting by adeno-associated viral vectors.

Microglia play a crucial role in maintaining homeostasis of the central nervous system and they are actively involved in shaping the brain's inflammatory response to stress. Among the multitude of involved molecules, purinergic receptors and enzymes are of special importance due to their ability to regulate microglia activation. By investigating the mechanisms underlying microglial responses and dysregulation, researchers can develop more precise interventions to modulate microglial behavior and alleviate neuroinflammatory processes. Studying gene function selectively in microglia, however, remains technically challenging. This review article provides an overview of adeno-associated virus (AAV)-based microglia targeting approaches, discussing potential prospects for refining these approaches to improve both specificity and effectiveness and encouraging future investigations aimed at connecting the potential of AAV-mediated microglial targeting for therapeutic benefit in neurological disorders.

Stamataki M ，Rissiek B ，Magnus T ，Körbelin J ... -  《Frontiers in Immunology》

A comprehensive review of AAV-mediated strategies targeting microglia for therapeutic intervention of neurodegenerative diseases.

Zhou L ，Wang Y ，Xu Y ，Zhang Y ，Zhu C ... -  《Journal of Neuroinflammation》

Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors.

Cucchiarini M ，Ren XL ，Perides G ，Terwilliger EF ... -  《GENE THERAPY》

Directed evolution of adeno-associated virus for efficient gene delivery to microglia.

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, Ca2+ 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.

Lin R ，Zhou Y ，Yan T ，Wang R ，Li H ，Wu Z ，Zhang X ，Zhou X ，Zhao F ，Zhang L ，Li Y ，Luo M ... -  《-》

Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges.

Maes ME ，Colombo G ，Schulz R ，Siegert S ... -  《-》