Design of time-delayed safety switches for CRISPR gene therapy

Abstract CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elim...

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Autor principal:	Dashan Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c208778be87c453c8b14d22081acd8d8
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spelling	oai:doaj.org-article:c208778be87c453c8b14d22081acd8d82021-12-02T16:46:34ZDesign of time-delayed safety switches for CRISPR gene therapy10.1038/s41598-021-96510-52045-2322https://doaj.org/article/c208778be87c453c8b14d22081acd8d82021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96510-5https://doaj.org/toc/2045-2322Abstract CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elimination systems, time-delayed safety switches are designed in this work. Firstly, ultrasensitive relationship is constructed between Cas9-sgRNA (enzyme) and Cas9 plasmids (substrate), which generates the artificial time delay. Then intrinsic time delay in biomolecular activities is revealed by data fitting and utilized in constructing safety switches. The time-delayed safety switches function by separating the gene editing process and self-elimination process, and the tunable delay time may ensure a good balance between gene editing efficiency and side effect minimization. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.Dashan SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dashan Sun Design of time-delayed safety switches for CRISPR gene therapy
description	Abstract CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elimination systems, time-delayed safety switches are designed in this work. Firstly, ultrasensitive relationship is constructed between Cas9-sgRNA (enzyme) and Cas9 plasmids (substrate), which generates the artificial time delay. Then intrinsic time delay in biomolecular activities is revealed by data fitting and utilized in constructing safety switches. The time-delayed safety switches function by separating the gene editing process and self-elimination process, and the tunable delay time may ensure a good balance between gene editing efficiency and side effect minimization. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.
format	article
author	Dashan Sun
author_facet	Dashan Sun
author_sort	Dashan Sun
title	Design of time-delayed safety switches for CRISPR gene therapy
title_short	Design of time-delayed safety switches for CRISPR gene therapy
title_full	Design of time-delayed safety switches for CRISPR gene therapy
title_fullStr	Design of time-delayed safety switches for CRISPR gene therapy
title_full_unstemmed	Design of time-delayed safety switches for CRISPR gene therapy
title_sort	design of time-delayed safety switches for crispr gene therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c208778be87c453c8b14d22081acd8d8
work_keys_str_mv	AT dashansun designoftimedelayedsafetyswitchesforcrisprgenetherapy
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Design of time-delayed safety switches for CRISPR gene therapy

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