KALA和REV细胞穿透肽在体外/体内传递HPV多表位DNA结构的效力研究。

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Haleh Feyzyab, Alireza Milani, Elnaz Agi, Mehrdad Hashemi, Azam Bolhassani
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引用次数: 0

摘要

开发人乳头瘤病毒(HPV)治疗性DNA疫苗需要一种有效的递送系统,如细胞穿透肽(CPPs)。本研究利用不同性质的KALA和REV CPPs体外和体内传递含有HPV16/18的L1、L2和E7蛋白免疫原性和保守性表位的多表位DNA构建体(pcDNA-L1-L2-E7和pEGFP-L1-L2-E7)。在此,在确认REV/DNA和KALA/DNA复合物后,研究了它们对DNA酶I和血清蛋白酶的稳定性。然后用定性和定量方法分析它们进入HEK-293T真核细胞的情况。最后,在C57BL/6小鼠模型上研究了肽/DNA复合物的抗肿瘤作用。根据获得的数据,REV/DNA和KALA/DNA复合物在N/P比为5:1时成功渗透到HEK-293T细胞中。此外,体内研究表明REV/DNA复合物(存活率:75%)和KALA/DNA复合物(存活率:50%)对小鼠C3肿瘤具有显著的保护作用。事实上,在C3攻击后50天,REV CPP比KALA CPP表现出更高的存活率和更小的肿瘤体积。这些发现代表了KALA和REV CPPs的潜力,特别是REV,作为开发HPV治疗性DNA候选疫苗的有希望的基因传递系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigation of the Potency of KALA and REV Cell-Penetrating Peptides for In Vitro/In Vivo Delivery of an HPV Multiepitope DNA Construct

Investigation of the Potency of KALA and REV Cell-Penetrating Peptides for In Vitro/In Vivo Delivery of an HPV Multiepitope DNA Construct

Developing human papillomavirus (HPV) therapeutic DNA vaccines requires an effective delivery system, such as cell-penetrating peptides (CPPs). In the current study, the multiepitope DNA constructs harboring the immunogenic and conserved epitopes of the L1, L2, and E7 proteins of HPV16/18 (pcDNA-L1-L2-E7 and pEGFP-L1-L2-E7) were delivered using KALA and REV CPPs with different properties in vitro and in vivo. Herein, after confirmation of the REV/DNA and KALA/DNA complexes, their stability was investigated against DNase I and serum protease. Then, their entry into HEK-293T eukaryotic cells was analyzed by qualitative and quantitative methods. Finally, anti-tumor effects of the peptide/DNA complexes were investigated in the C57BL/6 mouse model. Based on the obtained data, the REV/DNA and KALA/DNA complexes at the N/P ratio of 5:1 demonstrated successful penetration into HEK-293T cells. Furthermore, in vivo studies represented that the REV/DNA (survival rate: 75%) and KALA/DNA (survival rate: 50%) complexes provided significant protection against C3 tumors in mice. Indeed, REV CPP exhibited a higher survival rate and lower tumor volume than KALA CPP, 50 days after the C3 challenge. These findings represented the potential of KALA and REV CPPs, especially REV, as promising gene delivery systems for developing HPV therapeutic DNA vaccine candidates.

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来源期刊
Journal of Peptide Science
Journal of Peptide Science 生物-分析化学
CiteScore
3.40
自引率
4.80%
发文量
83
审稿时长
1.7 months
期刊介绍: The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.
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