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Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing

[Image: see text] We synthesized a series of poly(disulfide)s by ring-opening polymerization and demonstrated that the copolymerization of monomer 1 containing diethylenetriamine moieties and monomer 2 containing guanidyl ligands could generate an efficient delivery platform for different forms of C...

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Autores principales: Guo, Jiajing, Wan, Tao, Li, Bowen, Pan, Qi, Xin, Huhu, Qiu, Yayu, Ping, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227594/
https://www.ncbi.nlm.nih.gov/pubmed/34235260
http://dx.doi.org/10.1021/acscentsci.0c01648
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author Guo, Jiajing
Wan, Tao
Li, Bowen
Pan, Qi
Xin, Huhu
Qiu, Yayu
Ping, Yuan
author_facet Guo, Jiajing
Wan, Tao
Li, Bowen
Pan, Qi
Xin, Huhu
Qiu, Yayu
Ping, Yuan
author_sort Guo, Jiajing
collection PubMed
description [Image: see text] We synthesized a series of poly(disulfide)s by ring-opening polymerization and demonstrated that the copolymerization of monomer 1 containing diethylenetriamine moieties and monomer 2 containing guanidyl ligands could generate an efficient delivery platform for different forms of CRISPR-Cas9-based genome editors, including plasmid, mRNA, and protein. The excellent delivery performance of designed poly(disulfide)s stems from their delicate molecular structures to interact with genome-editing biomacromolecules, unique delivery pathways to mediate the cellular uptake of CRISPR-Cas9 cargoes, and strong ability to escape the endosome. The degradation of poly(disulfide)s by intracellular glutathione not only promotes the timely release of CRISPR-Cas9 machineries into the cytosol but also minimizes the cytotoxicity that nondegradable polymeric carriers often encounter. These merits collectively account for the excellent ability of poly(disulfide)s to mediate different forms of CRISPR-Cas9 for their efficient genome-editing activities in vitro and in vivo.
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spelling pubmed-82275942021-07-06 Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing Guo, Jiajing Wan, Tao Li, Bowen Pan, Qi Xin, Huhu Qiu, Yayu Ping, Yuan ACS Cent Sci [Image: see text] We synthesized a series of poly(disulfide)s by ring-opening polymerization and demonstrated that the copolymerization of monomer 1 containing diethylenetriamine moieties and monomer 2 containing guanidyl ligands could generate an efficient delivery platform for different forms of CRISPR-Cas9-based genome editors, including plasmid, mRNA, and protein. The excellent delivery performance of designed poly(disulfide)s stems from their delicate molecular structures to interact with genome-editing biomacromolecules, unique delivery pathways to mediate the cellular uptake of CRISPR-Cas9 cargoes, and strong ability to escape the endosome. The degradation of poly(disulfide)s by intracellular glutathione not only promotes the timely release of CRISPR-Cas9 machineries into the cytosol but also minimizes the cytotoxicity that nondegradable polymeric carriers often encounter. These merits collectively account for the excellent ability of poly(disulfide)s to mediate different forms of CRISPR-Cas9 for their efficient genome-editing activities in vitro and in vivo. American Chemical Society 2021-05-27 2021-06-23 /pmc/articles/PMC8227594/ /pubmed/34235260 http://dx.doi.org/10.1021/acscentsci.0c01648 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Guo, Jiajing
Wan, Tao
Li, Bowen
Pan, Qi
Xin, Huhu
Qiu, Yayu
Ping, Yuan
Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title_full Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title_fullStr Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title_full_unstemmed Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title_short Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing
title_sort rational design of poly(disulfide)s as a universal platform for delivery of crispr-cas9 machineries toward therapeutic genome editing
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227594/
https://www.ncbi.nlm.nih.gov/pubmed/34235260
http://dx.doi.org/10.1021/acscentsci.0c01648
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