Review of PF14 Analogs: Cell-Penetrating Peptides for Nucleic Acid Delivery

Abstract

Effective nucleic acid based drug delivery is a key challenge in translating gene therapy to clinical practice. Cell-penetrating peptides are the promising tool for delivery of nucleic-acid-based therapeutics into the cells both in vivo and in vitro. New analogs of the well-known CPP - PepFect14 - were created by fatty acid and amino acid residue modifications with the aim of optimizing complexation of CPPs with nucleic acids, stability of CPP/siRNA complexes and efficacy of transfection in the glioblastoma cell line - U87MG. Computational methods, Luciferase expression for evaluation of transfection efficiency, complexation and stability measurements by nucleic acid intercalating dyes, dynamic light scattering analysis, zeta potential measurements and viability assays were implemented for comprehensive research of the PF14 analogs. The study revealed two PF14 analogs, that formed well-defined nanoparticles with siRNA, which were stable against degradation, efficient for siRNA transfection, and didnot impair cell viability.