Synthesis and Application of Peptide-siRNA Nanoparticles from Disulfide-Constrained Cyclic Amphipathic Peptides for the Functional Delivery of Therapeutic Oligonucleotides to the Lung.

Abstract

The potential of RNAi therapies has been largely impeded by the inherent challenges in the functional delivery of siRNA to cells. Herein, we describe protocols for the synthesis and characterization of novel peptide-siRNA nanoparticles prepared from disulfide-constrained amphipathic peptides complexed with siRNA as promising siRNA delivery vectors. We also describe protocols for the application of these nanoparticles to the in vitro and in vivo delivery of siRNA to lung cells for the functional knockdown of lung proteins.