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      GMOs or non-GMOs? The CRISPR Conundrum

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          Abstract

          CRISPR-Cas9, the “genetic scissors”, is being presaged as a revolutionary technology, having tremendous potential to create designer crops by introducing precise and targeted modifications in the genome to achieve global food security in the face of climate change and increasing population. Traditional genetic engineering relies on random and unpredictable insertion of isolated genes or foreign DNA elements into the plant genome. However, CRISPR-Cas based gene editing does not necessarily involve inserting a foreign DNA element into the plant genome from different species but introducing new traits by precisely altering the existing genes. CRISPR edited crops are touching markets, however, the world community is divided over whether these crops should be considered genetically modified (GM) or non-GM. Classification of CRISPR edited crops, especially transgene free crops as traditional GM crops, will significantly affect their future and public acceptance in some regions. Therefore, the future of the CRISPR edited crops is depending upon their regulation as GM or non-GMs, and their public perception. Here we briefly discuss how CRISPR edited crops are different from traditional genetically modified crops. In addition, we discuss different CRISPR reagents and their delivery tools to produce transgene-free CRISPR edited crops. Moreover, we also summarize the regulatory classification of CRISPR modifications and how different countries are regulating CRISPR edited crops. We summarize that the controversy of CRISPR-edited plants as GM or non-GM will continue until a universal, transparent, and scalable regulatory framework for CRISPR-edited plants will be introduced worldwide, with increased public awareness by involving all stakeholders.

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          Most cited references86

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          Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage

          Summary The spontaneous deamination of cytosine is a major source of C•G to T•A transitions, which account for half of known human pathogenic point mutations. The ability to efficiently convert target A•T base pairs to G•C therefore could advance the study and treatment of genetic diseases. While the deamination of adenine yields inosine, which is treated as guanine by polymerases, no enzymes are known to deaminate adenine in DNA. Here we report adenine base editors (ABEs) that mediate conversion of A•T to G•C in genomic DNA. We evolved a tRNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs (e.g., ABE7.10), that convert target A•T to G•C base pairs efficiently (~50% in human cells) with very high product purity (typically ≥ 99.9%) and very low rates of indels (typically ≤ 0.1%). ABEs introduce point mutations more efficiently and cleanly than a current Cas9 nuclease-based method, induce less off-target genome modification than Cas9, and can install disease-correcting or disease-suppressing mutations in human cells. Together with our previous base editors, ABEs advance genome editing by enabling the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage.
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            Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors

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              Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

              Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)–Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.
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                Author and article information

                Contributors
                Journal
                Front Plant Sci
                Front Plant Sci
                Front. Plant Sci.
                Frontiers in Plant Science
                Frontiers Media S.A.
                1664-462X
                09 October 2023
                2023
                : 14
                : 1232938
                Affiliations
                [1] 1 Center for Advanced Studies in Agriculture and Food Security (CASAFS), University of Agriculture Faisalabad , Faisalabad, Pakistan
                [2] 2 Department of Biochemistry, University of Agriculture , Faisalabad, Pakistan
                [3] 3 Department of Chemistry, College of Science, United Arab Emirates University , Al-Ain, United Arab Emirates
                Author notes

                Edited by: Pejman Azadi, Agricultural Biotechnology Research Institute of Iran, Iran

                Reviewed by: Agata Tyczewska, Polish Academy of Sciences, Poland; Sang-Tae Kim, The Catholic University of Korea, Republic of Korea

                *Correspondence: Amer Jamil, amerjamil@ 123456yahoo.com ; Nayla Munawar, nmunawar@ 123456uaeu.ac.ae
                Article
                10.3389/fpls.2023.1232938
                10591184
                37877083
                0e27e8ab-fe98-4431-963f-5e3c441c476f
                Copyright © 2023 Ahmad, Jamil and Munawar

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 June 2023
                : 15 September 2023
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 90, Pages: 10, Words: 5887
                Funding
                NM’s research is funded by United Arab Emirates University (UAEU) UPAR 2022 research grant 12S094.
                Categories
                Plant Science
                Mini Review
                Custom metadata
                Plant Biotechnology

                Plant science & Botany
                crispr-cas,gene editing,gmos,gm regulations,transgenic plants
                Plant science & Botany
                crispr-cas, gene editing, gmos, gm regulations, transgenic plants

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