Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine
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Published:2023-11
Issue:11
Volume:88
Page:1800-1817
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ISSN:0006-2979
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Container-title:Biochemistry (Moscow)
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language:en
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Short-container-title:Biochemistry Moscow
Author:
Timotievich Ekaterina D.,Shilovskiy Igor P.,Khaitov Musa R.
Abstract
Abstract
Currently, nucleic acid therapeutics are actively developed for the treatment and prophylactic of metabolic disorders and oncological, inflammatory, and infectious diseases. A growing number of approved nucleic acid-based drugs evidences a high potential of gene therapy in medicine. Therapeutic nucleic acids act in the cytoplasm, which makes the plasma membrane the main barrier for the penetration of nucleic acid-based drugs into the cell and requires development of special vehicles for their intracellular delivery. The optimal carrier should not only facilitate internalization of nucleic acids, but also exhibit no toxic effects, ensure stabilization of the cargo molecules, and be suitable for a large-scale and low-cost production. Cell-penetrating peptides (CPPs), which match all these requirements, were found to be efficient and low-toxic carriers of nucleic acids. CPPs are typically basic peptides with a positive charge at physiological pH that can form nanostructures with negatively charged nucleic acids. The prospects of CPPs as vehicles for the delivery of therapeutic nucleic acids have been demonstrated in numerous preclinical studies. Some CPP-based drugs had successfully passed clinical trials and were implemented into medical practice. In this review, we described different types of therapeutic nucleic acids and summarized the data on the use of CPPs for their intracellular delivery, as well as discussed, the mechanisms of CPP uptake by the cells, as understanding of these mechanisms can significantly accelerate the development of new gene therapy approaches.
Publisher
Pleiades Publishing Ltd
Subject
Biochemistry,General Medicine,Biochemistry, Genetics and Molecular Biology (miscellaneous),Biophysics,Geriatrics and Gerontology
Reference78 articles.
1. Chaudhary, N., Weissman, D., and Whitehead, K. A. (2021) mRNA vaccines for infectious diseases: principles, delivery and clinical translation, Nat. Rev. Drug Discov., 20, 817-838,
https://doi.org/10.1038/S41573-021-00283-5. 2. Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., and van der Meel, R. (2021) The current landscape of nucleic acid therapeutics, Nat. Nanotechnol., 16, 630-643,
https://doi.org/10.1038/s41565-021-00898-0. 3. Talap, J., Zhao, J., Shen, M., Song, Z., Zhou, H., Kang, Y., Sun, L., Yu, L., Zeng, S., and Cai, S. (2021) Recent advances in therapeutic nucleic acids and their analytical methods, J. Pharm. Biomed. Anal., 206, 114368,
https://doi.org/10.1016/J.JPBA.2021.114368. 4. Wang, Y., Zhang, R., Tang, L., and Yang, L. (2022) Nonviral delivery systems of mRNA vaccines for cancer gene therapy, Pharmaceutics, 14, 512,
https://doi.org/10.3390/PHARMACEUTICS14030512. 5. Shirley, J. L., de Jong, Y. P., Terhorst, C., and Herzog, R. W. (2020) Immune responses to viral gene therapy vectors, Mol. Ther., 28, 709-722,
https://doi.org/10.1016/J.YMTHE.2020.01.001.
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