miRNA controlled vectors

miRNA restricted transgene expression

Micro RNAs (miRNA) are small, non-coding RNA molecules, which play a key role in the regulation of gene expression. So far, >1000 mature miRNAs have been described, and constantly new sequences are discovered (for details see www.mirbase.org). The miRNA expression profile and the individual level differs between distinct tissues and differential developmental stages, but also between cancerous and normal tissues. This difference can also be utilized when developing gene vectors for tissue- or tumor restricted transgene expression. When incorporating binding sites for distinct miRNAs into the expression cassette of a transgene, its expression will only take place in cells where the specific miRNA is diminished or absent. In this project we utilize the fact that miRNA 143, which is ubiquitously expressed in healthy tissue, is downregulated or absent in many cancers. For this purpose we have developed plasmid vectors, which carry multiple binding sites for miRNA143 between the 3’UTR of the transgene cDNA and the polyA signal. With this setup we are able to restrict the expression of reportergenes and therapeutically relevant transgenes to cancer cells with low or absent miRNA143 expression both in vitro and in transplanted tumor models in vivo.

 

References