Ubiquitous and Brain Cell-Type-Specific Promoters and Enhancers in Lentiviral Vectors

This chapter discusses the development and application of constitutive and brain cell-type-specific promoters and enhancers in lentiviral vectors to enable precise and efficient gene delivery. The fundamental mechanisms of transcriptional regulation by promoters, distinguished between constitutive and cell-type-specific promoters, are outlined and the role of enhancers in modulating transcriptional activity is emphasized. Recent breakthroughs in single-cell transcriptomics and assay for transposase-accessible chromatin (ATAC) sequencing have led to the identification of novel enhancer regions, thus paving the way for the development of more refined and targeted lentiviral vectors. These advances have the potential to significantly improve the specificity and efficacy of transgene expression in distinct brain cell populations, including excitatory and inhibitory neurons, astrocytes, and microglia.