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      Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections

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          Abstract

          Viral infections are a common cause of morbidity worldwide. The emergence of Coronavirus Disease 2019 (COVID-19) has led to more attention to viral infections and finding novel therapeutics. The CRISPR-Cas9 system has been recently proposed as a potential therapeutic tool for the treatment of viral diseases. Here, we review the research progress in the use of CRISPR-Cas technology for treating viral infections, as well as the strategies for improving the delivery of this gene-editing tool in vivo. Key challenges that hinder the widespread clinical application of CRISPR-Cas9 technology are also discussed, and several possible directions for future research are proposed.

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          CRISPR-Cas12–based detection of SARS-CoV-2

          James Broughton, Xianding Deng, Guixia Yu … (2020)
          An outbreak of betacoronavirus SARS-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from US patients, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US CDC SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.. SARS-CoV-2 in patient samples is detected in under an hour using a CRISPR-based lateral flow assay.
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            Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system.

            Bernd Zetsche, Jonathan S. Gootenberg, Omar Abudayyeh … (2015)
            The microbial adaptive immune system CRISPR mediates defense against foreign genetic elements through two classes of RNA-guided nuclease effectors. Class 1 effectors utilize multi-protein complexes, whereas class 2 effectors rely on single-component effector proteins such as the well-characterized Cas9. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we identified two candidate enzymes from Acidaminococcus and Lachnospiraceae, with efficient genome-editing activity in human cells. Identifying this mechanism of interference broadens our understanding of CRISPR-Cas systems and advances their genome editing applications.
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              Development and applications of CRISPR-Cas9 for genome engineering.

              Patrick D Hsu, Eric S. Lander, Feng Zhang (2014)
              Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of mammalian genome function. Analogous to the search function in modern word processors, Cas9 can be guided to specific locations within complex genomes by a short RNA search string. Using this system, DNA sequences within the endogenous genome and their functional outputs are now easily edited or modulated in virtually any organism of choice. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes. In this Review, we describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions. Derived from a remarkable microbial defense system, Cas9 is driving innovative applications from basic biology to biotechnology and medicine. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Pharmacother
                Journal ID (iso-abbrev): Biomed Pharmacother
                Title: Biomedicine & Pharmacotherapy
                Publisher: The Author(s). Published by Elsevier Masson SAS.
                ISSN (Print): 0753-3322
                ISSN (Electronic): 1950-6007
                Publication date PMC-release: 25 February 2022
                Publication date (Print): April 2022
                Publication date (Electronic): 25 February 2022
                Volume: 148
                Page: 112743
                Affiliations
                [a ]Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [b ]UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                [c ]Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [d ]Central Research Laboratory, Jahrom University of Medical Sciences, Jahrom, Iran
                [e ]Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
                [f ]Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [g ]Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
                [h ]Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
                [i ]Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
                [j ]Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Correspondence to: Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19395-4818, Iran.
                [** ]Corresponding author at: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
                [1]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: S0753-3322(22)00131-7 Publisher ID: 112743
                DOI: 10.1016/j.biopha.2022.112743
                PMC ID: 8872819
                PubMed ID: 35228065
                SO-VID: 056bdcf6-6453-4aa1-a7a0-6f1796f5ac0a
                Copyright © © 2022 The Authors
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 13 January 2022
                Date revision received : 16 February 2022
                Date accepted : 18 February 2022
                Categories
                Subject: Review

                Keywords: crispr-cas,gene editing,infection,treatment,virus
                Data availability:
                Keywords: crispr-cas, gene editing, infection, treatment, virus

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