Drug delivery agent that acts as a drug for synergistic activity

Drug delivery vehicles increase cell permeability of their cargo, but otherwise are expected to be inert. In developing a potential strategy to treat myotonic dystrophy type 1, we developed a delivery vehicle that was designed to be a direct acting drug. The oligomeric delivery agent selectively targets the expanded DNA and RNA repeat sequences (d(CTG)^exp and r(CUG)^exp) that cause DM1. By forming polyplexes with a locked nucleic acid CAG16 gapmer, that targets r(CUG)^exp, the polyplex facilitates cellular uptake of the LNA in HeLa cells, DM1 patient myoblasts, and the skeletal muscle of DM1 mice leading to phenotypic improvements in the in vitro DM1 models. Although the in vivo results are mixed, the overall results suggest the potential of a new strategy where both drug and delivery agent actively target a disease pathology.