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Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells
Since mitochondria contribute to tumorigenesis and drug resistance in cancer, mitochondrial genetic engineering promises a new direction for cancer therapy. Here, we report the use of the perimitochondrial enzymatic noncovalent synthesis (ENS) of peptides for delivering genes selectively into the mi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839975/ https://www.ncbi.nlm.nih.gov/pubmed/33511360 http://dx.doi.org/10.1016/j.xcrp.2020.100270 |
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author | He, Hongjian Lin, Xinyi Wu, Difei Wang, Jiaqing Guo, Jiaqi Green, Douglas R. Zhang, Hongwei Xu, Bing |
author_facet | He, Hongjian Lin, Xinyi Wu, Difei Wang, Jiaqing Guo, Jiaqi Green, Douglas R. Zhang, Hongwei Xu, Bing |
author_sort | He, Hongjian |
collection | PubMed |
description | Since mitochondria contribute to tumorigenesis and drug resistance in cancer, mitochondrial genetic engineering promises a new direction for cancer therapy. Here, we report the use of the perimitochondrial enzymatic noncovalent synthesis (ENS) of peptides for delivering genes selectively into the mitochondria of cancer cells for mitochondrial genetic engineering. Specifically, the micelles of peptides bind to the voltage-dependent anion channel (VDAC) on mitochondria for the proteolysis by enterokinase (ENTK), generating perimitochondrial nanofibers in cancer cells. This process, facilitating selective delivery of nucleic acid or gene vectors into mitochondria of cancer cells, enables the mitochondrial transgene expression of CRISPR/Cas9, FUNDC1, p53, and fluorescent proteins. Mechanistic investigation indicates that the interaction of the peptide assemblies with the VDAC and mitochondrial membrane potential are necessary for mitochondria targeting. This local enzymatic control of intermolecular noncovalent interactions enables selective mitochondrial genetic engineering, thus providing a strategy for targeting cancer cells. |
format | Online Article Text |
id | pubmed-7839975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-78399752021-01-27 Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells He, Hongjian Lin, Xinyi Wu, Difei Wang, Jiaqing Guo, Jiaqi Green, Douglas R. Zhang, Hongwei Xu, Bing Cell Rep Phys Sci Article Since mitochondria contribute to tumorigenesis and drug resistance in cancer, mitochondrial genetic engineering promises a new direction for cancer therapy. Here, we report the use of the perimitochondrial enzymatic noncovalent synthesis (ENS) of peptides for delivering genes selectively into the mitochondria of cancer cells for mitochondrial genetic engineering. Specifically, the micelles of peptides bind to the voltage-dependent anion channel (VDAC) on mitochondria for the proteolysis by enterokinase (ENTK), generating perimitochondrial nanofibers in cancer cells. This process, facilitating selective delivery of nucleic acid or gene vectors into mitochondria of cancer cells, enables the mitochondrial transgene expression of CRISPR/Cas9, FUNDC1, p53, and fluorescent proteins. Mechanistic investigation indicates that the interaction of the peptide assemblies with the VDAC and mitochondrial membrane potential are necessary for mitochondria targeting. This local enzymatic control of intermolecular noncovalent interactions enables selective mitochondrial genetic engineering, thus providing a strategy for targeting cancer cells. 2020-12-09 2020-12-23 /pmc/articles/PMC7839975/ /pubmed/33511360 http://dx.doi.org/10.1016/j.xcrp.2020.100270 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article He, Hongjian Lin, Xinyi Wu, Difei Wang, Jiaqing Guo, Jiaqi Green, Douglas R. Zhang, Hongwei Xu, Bing Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title | Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title_full | Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title_fullStr | Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title_full_unstemmed | Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title_short | Enzymatic Noncovalent Synthesis for Mitochondrial Genetic Engineering of Cancer Cells |
title_sort | enzymatic noncovalent synthesis for mitochondrial genetic engineering of cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839975/ https://www.ncbi.nlm.nih.gov/pubmed/33511360 http://dx.doi.org/10.1016/j.xcrp.2020.100270 |
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