# Purging Mutant mtDNA Using Mitochondrially‐Targeted Gamma Peptide Nucleic Acids

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $192,626

## Abstract

PROJECT SUMMARY
Numerous diseases arise from the presence of both normal and mutant forms of mitochondrial DNA (mtDNA).
Modest shifts in this heteroplasmy in favor of the normal mtDNA can have significant patient benefits. We
propose to use PNA oligomers to bind selectively to mutant mtDNA and block its replication, resulting in a
progressive shift in favor of normal mtDNA. PNA is the only synthetic oligonucleotide capable of binding to
any sequence of double-stranded DNA and has recently been validated to effectively target nuclear DNA in live
adult mice as well as in utero. We will functionalize PNAs with mitochondrial-penetrating peptides to promote
cell uptake and localization. PNA will be synthesized by standard solid phase methods, then characterized in
biophysical (gel mobility shift) and biochemical (inhibition of primer extension) experiments. PNA that exhibit
highest affinity and greatest potent blockage of polymerase activity will then be studied in cell culture, where
uptake, localization and phenotypic effects on heteroplasmy and mitochondrial oxygen consumption will be
determined.

## Key facts

- **NIH application ID:** 10000215
- **Project number:** 5R21HD099666-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Bruce A. ARMITAGE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,626
- **Award type:** 5
- **Project period:** 2019-08-22 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000215

## Citation

> US National Institutes of Health, RePORTER application 10000215, Purging Mutant mtDNA Using Mitochondrially‐Targeted Gamma Peptide Nucleic Acids (5R21HD099666-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10000215. Licensed CC0.

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