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

Methods Mol Biol. 2021:2208:49-67. doi: 10.1007/978-1-0716-0928-6_4.

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.

Keywords: Amphipathic peptide; Cyclic peptide; Nanoparticle; Oligonucleotide delivery; RNAi; siRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • A549 Cells
  • Cell Line, Tumor
  • Disulfides / chemistry*
  • Drug Delivery Systems / methods*
  • Gene Transfer Techniques
  • Humans
  • Lung / drug effects*
  • Nanoparticles / chemistry*
  • Oligonucleotides / chemistry*
  • Peptides, Cyclic / administration & dosage*
  • Peptides, Cyclic / chemistry*
  • RNA Interference / physiology
  • RNA, Small Interfering / chemistry*

Substances

  • Disulfides
  • Oligonucleotides
  • Peptides, Cyclic
  • RNA, Small Interfering