Development and Characterization of High Efficacy Cell-Penetrating Peptide via Modulation of the Histidine and Arginine Ratio for Gene Therapy
| Autor: | Huan-Huan Wan, Duo-Mei Tian, Yun-Sheng Xu, Xiao-Yong Zhan, Chang-Long Bi, Xiao-Jun Xu, Yu Liu, Bihui Huang, Le-Ping Yan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Technology
Genetic enhancement Peptide Gene delivery Endocytosis RALA peptide Article General Materials Science Histidine chemistry.chemical_classification Microscopy QC120-168.85 QH201-278.5 Transfection histidine Engineering (General). Civil engineering (General) gene therapy RALA Cell biology TK1-9971 chemistry cell penetrating peptide Descriptive and experimental mechanics Cell-penetrating peptide endosomal escaping Electrical engineering. Electronics. Nuclear engineering TA1-2040 |
| Zdroj: | Materials, Vol 14, Iss 4674, p 4674 (2021) Materials Volume 14 Issue 16 |
| ISSN: | 1996-1944 |
| Popis: | Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs. |
| Databáze: | OpenAIRE |
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