Transcriptional targeting to brain cells: Engineering cell type-specific promoter containing cassettes for enhanced transgene expression

Transcriptional targeting using a mammalian cellular promoter to restrict transgene expression to target cells is often desirable for gene therapy. This strategy is, however, hindered by relatively weak activity of some cellular promoters, which may lead to low levels of gene expression, thus declining therapeutic efficacy. Here we outline the advances accomplished in the area of transcriptional targeting to brain cells, with a particular focus on engineering gene cassettes to augment cell type-specific expression. Among the effective approaches that improve gene expression while retaining promoter specificity are promoter engineering to change authentic sequences of a cellular promoter and the combined use of a native cellular promoter and other cis-acting elements. Success in achieving high level and sustained transgene expression only in the cell types of interest would be of importance in allowing gene therapy to have its impact on patient treatment.