Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair

Molecules. 2020 Feb 8;25(3):735. doi: 10.3390/molecules25030735.


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.

Keywords: PNA; cystic fibrosis; gene editing; nanoparticles; peptide nucleic acids; recombination; repair; structure; triplex; β-thalassemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / therapy*
  • DNA / genetics*
  • DNA / metabolism
  • Disease Models, Animal
  • Gene Editing / methods*
  • Gene Targeting / methods
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism
  • Nucleic Acid Conformation
  • Nucleic Acid Hybridization
  • Peptide Nucleic Acids / administration & dosage
  • Peptide Nucleic Acids / genetics*
  • Peptide Nucleic Acids / metabolism
  • Recombinational DNA Repair
  • beta-Thalassemia / genetics
  • beta-Thalassemia / metabolism
  • beta-Thalassemia / pathology
  • beta-Thalassemia / therapy*


  • Peptide Nucleic Acids
  • DNA