Use of adeno-associated viruses for transgenic modulation of microglia structure and function: A review of technical considerations and challenges.

• AAV constructs express transgenes in CNS cells, but microglia present challenges. • Novel, genetically modified AAV capsids show improved microglial transduction. • Myeloid-specific promoters in AAV constructs fail to prevent off-target expression. • Microscopy and PCR controls may minimize false positive AAV transgene detection. Microglia play a central role in the etiology of many neuropathologies. Transgenic tools are a powerful experiment approach to gain reliable and specific control over microglia function. Adeno-associated virus (AAVs) vectors are already an indispensable tool in neuroscience research. Despite ubiquitous use of AAVs and substantial interest in the role of microglia in the study of central nervous system (CNS) function and disease, transduction of microglia using AAVs is seldom reported. This review explores the challenges and advancements made in using AAVs for expressing transgenes in microglia. First, we will examine the functional anatomy of the AAV capsid, which will serve as a basis for subsequent discussions of studies exploring the relationship between capsid mutations and microglia transduction efficacy. After outlining the functional anatomy of AAVs, we will consider the experimental evidence demonstrating AAV-mediated transduction of microglia and microglia-like cell lines followed by an examination of the most promising experimental approaches identified in the literature. Finally, technical limitations will be considered in future applications of AAV experimental approaches. [ABSTRACT FROM AUTHOR]