Elastin-Derived VGVAPG Fragment Decorated Cell-Penetrating Peptide with Improved Gene Delivery Efficacy

作者：Shen, Wen-Juan; Tian, Duo-Mei; Fu, Le; Jin, Biao; Liu, Yu; Xu, Yun-Sheng; Ye, Yong-Bin; Wang, Xiao-Bo; Xu, Xiao-Jun; Tang, Chun; Li, Fang-Ping; Wang, Chun-Fei^*; Wu, Gang; Yan, Le-Ping^*

来源：Pharmaceutics, 2023, 15(2): 670.

DOI：10.3390/pharmaceutics15020670

• cell-penetrating peptide
• gene delivery
• elastin-derived peptide
• elastin-binding protein
• immune modulation

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and m beta CD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

• 单位
  中山大学