Alkylated RALA-Derived Peptides for Efficient Gene Delivery
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Updated: Jun 7, 2025

Peptide-derived Method to Transport Genes and Proteins Across Cellular and Organellar Barriers in Plants
Published on: December 16, 2016
Xuelin Zhang1, Yexi Zhang1, Xi Rong1
1State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.
Abstract:
RALA is an amphipathic cationic peptide demonstrated to be a low-toxicity and high-efficiency delivery platform for the systemic delivery of nucleic acid therapeutics. This work reports three RALA-derived peptides modified with N-terminal palmitic acid, engineered through amino acid substitutions and truncated sequences. All three peptides have good nucleic acid encapsulation, release and uptake, biocompatibility, and endolysosome escape. The siRNA transfection efficiency is about 90%, and the silencing rate of GA (C16-GLFWHHHARLARALARHLARALRA) exceeds that of lipofectamine 2000 (siRNA concentration = 50 nM). Truncating the peptide chain while retaining a certain amount of arginine ensures an effective particle size. Replacing glutamic acid with three histidines ensures an effective zeta potential and accelerates the endosome escape process through the proton sponge phenomenon. Introducing phenylalanine enhances the carrier-cell interaction. We believe that they are powerful carriers of siRNA therapy and may have good application prospects in treating various diseases.

