Advances in peptide nucleic acid for targeting RNA and genomic DNA

Angana De; Vikas Kumar; W. Mark Saltzman; Frank J. Slack; Ajit Vikram; Anisha Gupta; Raman Bahal

doi:10.1016/j.xcrp.2025.103061

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Advances in peptide nucleic acid for targeting RNA and genomic DNA

Journal article

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Peer reviewed

Advances in peptide nucleic acid for targeting RNA and genomic DNA

Angana De, Vikas Kumar, W. Mark Saltzman, Frank J. Slack, Ajit Vikram, Anisha Gupta and Raman Bahal

Cell reports physical science, Vol.7(1), 103061

01/21/2026

DOI: 10.1016/j.xcrp.2025.103061

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Abstract

Peptide nucleic acid (PNA) is a synthetic mimic of DNA where the deoxyribose-phosphodiester backbone is replaced with N-(2-aminoethyl) glycine units. The lack of deoxyribose-phosphodiester bonds enhances enzymatic stability and improves binding affinity of PNA with complementary DNA and RNA strands. To enhance target binding, conformational stability, and pharmacological activity, several chemical modifications have been introduced into PNA. Modified PNAs have demonstrated promising preclinical potential as antisense and anti-gene agents, supporting their use in diverse biomedical applications. The limited in vivo biodistribution and cellular uptake of PNA have significantly hindered its clinical development. Enhancing PNA biodistribution using nanoformulations and bioconjugate-based delivery strategies has resulted in substantial in vivo pharmacological effects. Further, with advancements in chemistry and delivery techniques, PNA holds promise in treating genetic diseases, metabolic disorders, cancers, and infectious diseases. This review summarizes PNA's pharmacological mechanisms, chemical modifications, delivery strategies, and therapeutic applications while addressing limitations for clinical translation. [Display omitted] De et al. describe the current landscape of peptide nucleic acid (PNA) as a promising therapeutic nucleic acid advancing through preclinical development, driven by improvements in chemistry and delivery techniques. PNA’s growing application in genetic, metabolic, cancer, and infectious disease research emphasizes its translation potential from laboratory studies to clinical use.

RNA

anti-gene

antisense

gene editing

microRNA

peptide nucleic acid

Details

Title: Subtitle: Advances in peptide nucleic acid for targeting RNA and genomic DNA
Creators: Angana De - University of Connecticut
Vikas Kumar - University of Connecticut
W. Mark Saltzman - Yale University
Frank J. Slack - Beth Israel Deaconess Hospital
Ajit Vikram - University of Iowa
Anisha Gupta - University of Saint Joseph
Raman Bahal - University of Connecticut
Resource Type: Journal article
Publication Details: Cell reports physical science, Vol.7(1), 103061
DOI: 10.1016/j.xcrp.2025.103061
ISSN: 2666-3864
eISSN: 2666-3864
Publisher: Elsevier Inc
Grant note: National Institutes of Health: 1R01CA241194, HL167773
This work was funded by National Institutes of Health 1R01CA241194 to F.J.S. and R.B. and HL167773 to A.V. Figures were made using BioRender.com .
Language: English
Electronic publication date: 01/12/2026
Date published: 01/21/2026
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9985121597302771

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