Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/3/735 |
| id |
doaj-1457246a1487470b8e747bc56cd3198e |
|---|---|
| record_format |
Article |
| spelling |
doaj-1457246a1487470b8e747bc56cd3198e2020-11-25T02:03:24ZengMDPI AGMolecules1420-30492020-02-0125373510.3390/molecules25030735molecules25030735Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and RepairNicholas G. Economos0Stanley Oyaghire1Elias Quijano2Adele S. Ricciardi3W. Mark Saltzman4Peter M. Glazer5Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USADepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USADepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USAUnusual 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.https://www.mdpi.com/1420-3049/25/3/735peptide nucleic acidspnatriplexgene editingstructurerecombinationrepairnanoparticlesβ-thalassemiacystic fibrosis |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Nicholas G. Economos Stanley Oyaghire Elias Quijano Adele S. Ricciardi W. Mark Saltzman Peter M. Glazer |
| spellingShingle |
Nicholas G. Economos Stanley Oyaghire Elias Quijano Adele S. Ricciardi W. Mark Saltzman Peter M. Glazer Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair Molecules peptide nucleic acids pna triplex gene editing structure recombination repair nanoparticles β-thalassemia cystic fibrosis |
| author_facet |
Nicholas G. Economos Stanley Oyaghire Elias Quijano Adele S. Ricciardi W. Mark Saltzman Peter M. Glazer |
| author_sort |
Nicholas G. Economos |
| title |
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair |
| title_short |
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair |
| title_full |
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair |
| title_fullStr |
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair |
| title_full_unstemmed |
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair |
| title_sort |
peptide nucleic acids and gene editing: perspectives on structure and repair |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2020-02-01 |
| description |
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. |
| topic |
peptide nucleic acids pna triplex gene editing structure recombination repair nanoparticles β-thalassemia cystic fibrosis |
| url |
https://www.mdpi.com/1420-3049/25/3/735 |
| work_keys_str_mv |
AT nicholasgeconomos peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair AT stanleyoyaghire peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair AT eliasquijano peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair AT adelesricciardi peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair AT wmarksaltzman peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair AT petermglazer peptidenucleicacidsandgeneeditingperspectivesonstructureandrepair |
| _version_ |
1724948565947580416 |