Cell-penetrating peptides for in vitro delivery of small interfering RNA and splice-correcting oligonucleotides

Abstract

Optimization of carrier systems is required to enhance the development of nucleic acid therapies. Cell-penetrating peptides (CPPs) are promising transport vectors for this purpose, which can form nanoparticles with therapeutic nucleic acids and facilitate their transport to intracellular targets. As part of this work, the potential of five amphipathic PepFect14-based CPPs complexed with small interfering RNA (siRNA) and splice-correcting oligonucleotides (SCOs) was studied in the formation of nanoparticles and the delivery of nucleic acid into the cell. All new analogs tested formed CPP-nucleic acid complexes with both siRNA and SCOs. In addition, the stability of CPP/siRNA nanoparticles was tested against enzymatic degradation and polyanionic heparin. The four analogs possessed a suitable profile as siRNA transport vectors, while only two analogs were suitable as tested under the given conditions for both siRNA and SCO. None of the CPP/siRNA and CPP/SCO nanoparticles tested had a significant impact on cell viability.