A technique that promotes the stringent control of gene expression within specific cell types

Unmet Need

A major challenge of gene therapy is to target only the intended cell- and/or tissue-type. For this reason, many gene therapies are delivered using adeno-associated virus (AAV) vectors with gene-specific promoters; however, off-target AAV tropism and inadequate promoter regulation many times lead to the expression of the delivered gene in unintended cells or tissues. For these reasons, methods that can restrict the expression of the delivered gene within specific cells or tissues are needed for the safe implementation of gene therapy.

Technology

Duke inventors have developed a technique for gene therapies that promotes the stringent control of gene expression within specific cell types. This is achieved by combining gene-specific promoters with cell type-specific splicing exons and microRNA-binding sites. This invention has the potential to enhance the stringency of AAV-delivered gene therapies, or it could be utilized in stand-alone nucleic acid delivery systems (e.g. nanoparticle-, lipofection-, electroporation-mediated delivery). The latter would overcome several of the limitations of viral-based gene therapies, including immunological neutralization by the host and restrictions on transgene size. This technology has demonstrated greater expression differentials between cell types in the lab.

Advantages

• Offers spatiotemporal control of gene expression
• Prevents “leaky” expression in unintended cell types
• Could improve safety of gene therapies