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

•Background of lentiviral and adeno-associated virus vector design.•Reviewing of literature that reported in vivo microglial transduction.•Challenges to overcome low microglial transduction efficiency and specificity.•Guidelines for reporting viral transduction in microglia. Microglia have emerged as a critical component of neurodegenerative diseases. Genetic manipulation of microglia can elucidate their functional impact in disease. In neuroscience, recombinant viruses such as lentiviruses and adeno-associated viruses (AAVs) have been successfully used to target various cell types in the brain, although effective transduction of microglia is rare. In this review, we provide a short background of lentiviruses and AAVs, and strategies for designing recombinant viral vectors. Then, we will summarize recent literature on successful microglial transductions in vitro and in vivo, and discuss the current challenges. Finally, we provide guidelines for reporting the efficiency and specificity of viral targeting in microglia, which will enable the microglial research community to assess and improve methodologies for future studies.