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      Ethical considerations of gene editing and genetic selection

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      Author(s): , BA 1 ,
      Publication date (Electronic):
      Journal: Journal of General and Family Medicine
      Publisher: John Wiley and Sons Inc.
      Keywords: ethical, ethics, gene editing, genetic selection

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          Abstract

          For thousands of years, humans have felt the need to understand the world around them—and ultimately manipulate it to best serve their needs. There are always ethical questions to address, especially when the manipulation involves the human genome. There is currently an urgent need to actively pursue those conversations as commercial gene sequencing and editing technologies have become more accessible and affordable. This paper explores the ethical considerations of gene editing (specifically germline) and genetic selection—including the hurdles researchers will face in trying to develop new technologies into viable therapeutic options.

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          Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting

          Tomas Cermak, Erin L. Doyle, Michelle Christian … (2011)
          TALENs are important new tools for genome engineering. Fusions of transcription activator-like (TAL) effectors of plant pathogenic Xanthomonas spp. to the FokI nuclease, TALENs bind and cleave DNA in pairs. Binding specificity is determined by customizable arrays of polymorphic amino acid repeats in the TAL effectors. We present a method and reagents for efficiently assembling TALEN constructs with custom repeat arrays. We also describe design guidelines based on naturally occurring TAL effectors and their binding sites. Using software that applies these guidelines, in nine genes from plants, animals and protists, we found candidate cleavage sites on average every 35 bp. Each of 15 sites selected from this set was cleaved in a yeast-based assay with TALEN pairs constructed with our reagents. We used two of the TALEN pairs to mutate HPRT1 in human cells and ADH1 in Arabidopsis thaliana protoplasts. Our reagents include a plasmid construct for making custom TAL effectors and one for TAL effector fusions to additional proteins of interest. Using the former, we constructed de novo a functional analog of AvrHah1 of Xanthomonas gardneri. The complete plasmid set is available through the non-profit repository AddGene and a web-based version of our software is freely accessible online.
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            Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements.

            Francisco Mojica, César Díez-Villaseñor, Jesús García-Martínez … (2005)
            Prokaryotes contain short DN repeats known as CRISPR, recognizable by the regular spacing existing between the recurring units. They represent the most widely distributed family of repeats among prokaryotic genomes suggesting a biological function. The origin of the intervening sequences, at present unknown, could provide clues about their biological activities. Here we show that CRISPR spacers derive from preexisting sequences, either chromosomal or within transmissible genetic elements such as bacteriophages and conjugative plasmids. Remarkably, these extrachromosomal elements fail to infect the specific spacer-carrier strain, implying a relationship between CRISPR and immunity against targeted DNA. Bacteriophages and conjugative plasmids are involved in prokaryotic population control, evolution, and pathogenicity. All these biological traits could be influenced by the presence of specific spacers. CRISPR loci can be visualized as mosaics of a repeated unit, separated by sequences at some time present elsewhere in the cell.
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              Targeting DNA double-strand breaks with TAL effector nucleases.

              Michelle Christian, Tomas Cermak, Erin L. Doyle … (2010)
              Engineered nucleases that cleave specific DNA sequences in vivo are valuable reagents for targeted mutagenesis. Here we report a new class of sequence-specific nucleases created by fusing transcription activator-like effectors (TALEs) to the catalytic domain of the FokI endonuclease. Both native and custom TALE-nuclease fusions direct DNA double-strand breaks to specific, targeted sites.
              Article 0 comments Cited 627 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jodie Rothschild:
                ORCID: https://orcid.org/0000-0002-1596-5409
                rothschild.jodie@gmail.com
                Journal
                Journal ID (nlm-ta): J Gen Fam Med
                Journal ID (iso-abbrev): J Gen Fam Med
                Journal ID (doi): 10.1002/(ISSN)2189-7948
                Journal ID (publisher-id): JGF2
                Title: Journal of General and Family Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 2189-6577
                ISSN (Electronic): 2189-7948
                Publication date (Electronic): 29 May 2020
                Publication date Collection: May 2020
                Volume: 21
                Issue: 3 ( doiID: 10.1002/jgf2.v21.3 )
                Pages: 37-47
                Affiliations
                [ 1 ] Rothschild Biomedical Communications Seattle WA USA
                Author notes
                [*] [* ] Correspondence

                Jodie Rothschild, Rothschild Biomedical Communications, 7357 23rd Avenue Northeast, Seattle, WA 98115, USA.

                Email: rothschild.jodie@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-1596-5409
                Article
                Publisher ID: JGF2321
                DOI: 10.1002/jgf2.321
                PMC ID: 7260159
                PubMed ID: 32489755
                SO-VID: b45a1e11-a054-49fd-b2bf-6d672eae0e64
                Copyright © © 2020 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 31 March 2020
                Date accepted : 01 April 2020
                Page count
                Figures: 0, Tables: 0, Pages: 11, Words: 9537
                Categories
                Subject: Special Article
                Subject: Special Article
                Custom metadata
                source-schema-version-number 2.0
                cover-date May 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:29.05.2020

                Keywords: ethical,ethics,gene editing,genetic selection
                Data availability:
                Keywords: ethical, ethics, gene editing, genetic selection

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