PPMOs: A Case Study for Cell-Penetrating Peptide Application

The current state of the art for in vivo antisense morpholino technology is peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), offering unparalleled control over gene expression within living systems. PPMOs consist of an uncharged morpholino oligomer conjugated through a linker to a cell-penetrating peptide (CPP) and are designed to bind cellular RNAs through base complementarity. By sterically blocking cellular components that interact with targeted RNA, PPMOs can be used to inhibit translation, modulate splicing, block polyadenylation and inhibit microRNAs. This platform is readily adaptable to a wide variety of tasks, requiring only a change in sequence to move from one application to another. PPMOs have seen effective use within many contexts including genetic disease and viral, bacterial and parasitic infection. A PPMO is currently in clinical trials for the treatment of Duchenne muscular dystrophy. CPPs have been integral to the development of PPMOs.