Journal
MOLECULES
Volume 25, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/molecules25030735
Keywords
peptide nucleic acids; PNA; triplex; gene editing; structure; recombination; repair; nanoparticles; beta-thalassemia; cystic fibrosis
Funding
- NIGMS Medical Scientist Training Program [T32GM07205]
- National Heart, Lung and Blood Institute [1F30HL149185, F30HL134252, R01HL125892]
- NIGMS predoctoral training grant [5T32GM007223]
Ask authors/readers for more resources
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 beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available