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      Is Open Access

      How to talk about genome editing

      review-article
      British Medical Bulletin
      Oxford University Press
      genome editing, public understanding, DNA, CRISPR, fertility, embryo

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Human genome editing is an area of growing prominence, with many potential therapeutic applications.

          Sources of data

          A project by two UK charities, whose participants included fertility sector patients and practitioners and also people affected by genetic disease and rare disease. Scientific research into, and wider discussion of, genomics and genome editing.

          Areas of agreement

          There is a need for improved public and professional understanding of genome editing.

          Areas of controversy

          The way genome editing is discussed is often inconsistent and confusing. Simply defining and explaining the term ‘genome’ can present challenges.

          Growing points

          There are approaches that lend themselves to achieving greater clarity and coherence in discussion of genome editing.

          Areas timely for developing research

          People’s understanding should ideally be able to withstand and evolve alongside current developments in genome editing, rather than being tied firmly to specific aspects of genome editing (which may in future be supplanted).

          Related collections

          Most cited references23

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          STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES

          1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered. 2. Methods for the isolation and purification of the active transforming material are described. 3. The data obtained by chemical, enzymatic, and serological analyses together with the results of preliminary studies by electrophoresis, ultracentrifugation, and ultraviolet spectroscopy indicate that, within the limits of the methods, the active fraction contains no demonstrable protein, unbound lipid, or serologically reactive polysaccharide and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid. 4. Evidence is presented that the chemically induced alterations in cellular structure and function are predictable, type-specific, and transmissible in series. The various hypotheses that have been advanced concerning the nature of these changes are reviewed.
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            Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product.

            The iap gene in Escherichia coli is responsible for the isozyme conversion of alkaline phosphatase. We analyzed the 1,664-nucleotide sequence of a chromosomal DNA segment that contained the iap gene and its flanking regions. The predicted iap product contained 345 amino acids with an estimated molecular weight of 37,919. The 24-amino-acid sequence at the amino terminus showed features characteristic of a signal peptide. Two proteins of different sizes were identified by the maxicell method, one corresponding to the Iap protein and the other corresponding to the processed product without the signal peptide. Neither the isozyme-converting activity nor labeled Iap proteins were detected in the osmotic-shock fluid of cells carrying a multicopy iap plasmid. The Iap protein seems to be associated with the membrane.
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              In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans -epigenetic Modulation

              Current genome-editing systems generally rely on the creation of DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. The CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here we report a robust system for in vivo activation of endogenous target genes through trans -epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat several mouse models of human diseases. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo , leading to observable phenotypic changes, and amelioration of disease symptoms. This establishes new avenues for developing targeted epigenetic therapies against human diseases.
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                Author and article information

                Journal
                Br Med Bull
                Br. Med. Bull
                brimed
                British Medical Bulletin
                Oxford University Press
                0007-1420
                1471-8391
                June 2018
                25 April 2018
                25 April 2018
                : 126
                : 1
                : 5-12
                Affiliations
                Progress Educational Trust, 140 Grays Inn Road, London, UK
                Author notes
                Correspondence address. Progress Educational Trust, 140 Grays Inn Road, London WC1X 8AX, UK. E-mail: sstarr@ 123456progress.org.uk
                Article
                ldy015
                10.1093/bmb/ldy015
                5998984
                29697749
                4eaa034a-d601-4139-9dba-675a82eaa127
                © The Author(s) 2018. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 February 2018
                : 15 April 2018
                Page count
                Pages: 8
                Categories
                Invited Review
                Editor's Choice

                Medicine
                genome editing,public understanding,dna,crispr,fertility,embryo
                Medicine
                genome editing, public understanding, dna, crispr, fertility, embryo

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