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

Autor: Wen-Juan Shen, Duo-Mei Tian, Le Fu, Biao Jin, Yu Liu, Yun-Sheng Xu, Yong-Bin Ye, Xiao-Bo Wang, Xiao-Jun Xu, Chun Tang, Fang-Ping Li, Chun-Fei Wang, Gang Wu, Le-Ping Yan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceutics, Vol 15, Iss 2, p 670 (2023)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics15020670
Popis: 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 mβCD 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.
Databáze: Directory of Open Access Journals
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