Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair
Identifieur interne : 000079 ( an2020/Analysis ); précédent : 000078; suivant : 000080Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair
Auteurs : Nicholas G. Economos ; Stanley Oyaghire ; Elias Quijano ; Adele S. Ricciardi ; W. Mark Saltzman ; Peter M. GlazerSource :
- Molecules [ 1420-3049 ] ; 2020.
Abstract
Unusual nucleic acid structures are salient triggers of endogenous repair and can occur in sequence-specific contexts. Peptide nucleic acids (PNAs) rely on these principles to achieve non-enzymatic gene editing. By forming high-affinity heterotriplex structures within the genome, PNAs have been used to correct multiple human disease-relevant mutations with low off-target effects. Advances in molecular design, chemical modification, and delivery have enabled systemic in vivo application of PNAs resulting in detectable editing in preclinical mouse models. In a model of β-thalassemia, treated animals demonstrated clinically relevant protein restoration and disease phenotype amelioration, suggesting a potential for curative therapeutic application of PNAs to monogenic disorders. This review discusses the rationale and advances of PNA technologies and their application to gene editing with an emphasis on structural biochemistry and repair.
Url:
DOI: 10.3390/molecules25030735
PubMed: 32046275
PubMed Central: 7037966
Affiliations:
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PMC:7037966Le document en format XML
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Economos</name><affiliation><nlm:aff id="af1-molecules-25-00735">Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;<email>nicholas.economos@yale.edu</email> (N.G.E.);<email>elias.quijano@yale.edu</email> (E.Q.)</nlm:aff></affiliation></author><author><name sortKey="Oyaghire, Stanley" sort="Oyaghire, Stanley" uniqKey="Oyaghire S" first="Stanley" last="Oyaghire">Stanley Oyaghire</name><affiliation><nlm:aff id="af2-molecules-25-00735">Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA;<email>stanley.oyaghire@yale.edu</email></nlm:aff></affiliation></author><author><name sortKey="Quijano, Elias" sort="Quijano, Elias" uniqKey="Quijano E" first="Elias" last="Quijano">Elias Quijano</name><affiliation><nlm:aff id="af1-molecules-25-00735">Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;<email>nicholas.economos@yale.edu</email> (N.G.E.);<email>elias.quijano@yale.edu</email> (E.Q.)</nlm:aff></affiliation></author><author><name sortKey="Ricciardi, Adele S" sort="Ricciardi, Adele S" uniqKey="Ricciardi A" first="Adele S." last="Ricciardi">Adele S. 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Economos</name><affiliation><nlm:aff id="af1-molecules-25-00735">Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;<email>nicholas.economos@yale.edu</email> (N.G.E.);<email>elias.quijano@yale.edu</email> (E.Q.)</nlm:aff></affiliation></author><author><name sortKey="Oyaghire, Stanley" sort="Oyaghire, Stanley" uniqKey="Oyaghire S" first="Stanley" last="Oyaghire">Stanley Oyaghire</name><affiliation><nlm:aff id="af2-molecules-25-00735">Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA;<email>stanley.oyaghire@yale.edu</email></nlm:aff></affiliation></author><author><name sortKey="Quijano, Elias" sort="Quijano, Elias" uniqKey="Quijano E" first="Elias" last="Quijano">Elias Quijano</name><affiliation><nlm:aff id="af1-molecules-25-00735">Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;<email>nicholas.economos@yale.edu</email> (N.G.E.);<email>elias.quijano@yale.edu</email> (E.Q.)</nlm:aff></affiliation></author><author><name sortKey="Ricciardi, Adele S" sort="Ricciardi, Adele S" uniqKey="Ricciardi A" first="Adele S." last="Ricciardi">Adele S. Ricciardi</name><affiliation><nlm:aff id="af3-molecules-25-00735">Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA;<email>adele.ricciardi@yale.edu</email> (A.S.R.);<email>Mark.saltzman@yale.edu</email> (W.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Saltzman, W Mark" sort="Saltzman, W Mark" uniqKey="Saltzman W" first="W. Mark" last="Saltzman">W. Mark Saltzman</name><affiliation><nlm:aff id="af3-molecules-25-00735">Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA;<email>adele.ricciardi@yale.edu</email> (A.S.R.);<email>Mark.saltzman@yale.edu</email> (W.M.S.)</nlm:aff></affiliation></author><author><name sortKey="Glazer, Peter M" sort="Glazer, Peter M" uniqKey="Glazer P" first="Peter M." last="Glazer">Peter M. Glazer</name><affiliation><nlm:aff id="af1-molecules-25-00735">Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;<email>nicholas.economos@yale.edu</email> (N.G.E.);<email>elias.quijano@yale.edu</email> (E.Q.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-molecules-25-00735">Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA;<email>stanley.oyaghire@yale.edu</email></nlm:aff></affiliation></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Unusual nucleic acid structures are salient triggers of endogenous repair and can occur in sequence-specific contexts. Peptide nucleic acids (PNAs) rely on these principles to achieve non-enzymatic gene editing. By forming high-affinity heterotriplex structures within the genome, PNAs have been used to correct multiple human disease-relevant mutations with low off-target effects. Advances in molecular design, chemical modification, and delivery have enabled systemic in vivo application of PNAs resulting in detectable editing in preclinical mouse models. In a model of β-thalassemia, treated animals demonstrated clinically relevant protein restoration and disease phenotype amelioration, suggesting a potential for curative therapeutic application of PNAs to monogenic disorders. This review discusses the rationale and advances of PNA technologies and their application to gene editing with an emphasis on structural biochemistry and repair.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Watson, J D" uniqKey="Watson J">J.D. Watson</name></author><author><name sortKey="Crick, F H C" uniqKey="Crick F">F.H.C. 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Ricciardi</name><name sortKey="Saltzman, W Mark" sort="Saltzman, W Mark" uniqKey="Saltzman W" first="W. Mark" last="Saltzman">W. Mark Saltzman</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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