The 812850 2shRNA project has allowed us to create a new branched RNA nanostructure (2shRNA2) that overcomes Dicer recognition and that induces high antiproliferative levels in HER2+ breast cancer cells. This new branched design is a simplified version of our previously reported branched structure (2shRNA) and consists in two 19-nt guide strands (of the appropriate length for RISC recognition) that are base-paired to two sense strands that are linked together by an internal bulge. This new design is totally compatible with biostable modifications at internal positions, and thus, a good candidate for in vivo validation.
We are working now on the development of new lipid nanoparticles functionalized with peptides recognized by tumor receptors, for specific delivery of the 2shRNA2 structure to tumor cells.
