# To employ gamma-peptide nucleic acid oligomers to interfere with viral replication

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $195,166

## Abstract

PROJECT SUMMARY
 Seasonal influenza A viruses (IAV) cause millions of infections and thousands of deaths each year in the
US. Low vaccine efficacy and rapid antiviral resistance requires development of alternative therapeutic
strategies to limit the burden of influenza on the population. The genome of IAV consists of eight negative-
sense RNA segments that upon infection are first copied into positive-sense complementary RNA (cRNA),
which in turn are replicated into genomic negative-sense viral RNA (vRNA) segments that will be packaged
into progeny viruses. As the viral life cycle critically depends on template-mediated vRNA replication, an
appealing approach to halt virus multiplication would be to place complementary antisense oligonucleotides
(ASOs) as roadblocks on vRNA segments to stall viral polymerase progression.
 Our objective in this proposal is to examine the suitability of gamma-peptide nucleic acids (PNAs) as an
antiviral against influenza virus replication. Gamma-PNAs are second-generation analogues of PNAs that
show enhanced affinity, water solubility and biological activity when targeted to cellular RNA or genomic DNA.
As this modified backbone enhances the hybridization affinity with target RNAs by significantly increasing the
melting temperature of the resulting duplex, gamma-PNAs, unlike conventional DNA or RNA oligomers, could
indeed function as stable roadblocks for viral polymerase. We have assembled an interdisciplinary team with
expertise in the relevant areas, i.e. RNA biology, influenza virology, and PNA chemistry, to successfully
complete the proposed experiments. Taken together, our study will lay the groundwork for future in vivo
pharmacokinetic studies in animals.

## Key facts

- **NIH application ID:** 10108607
- **Project number:** 1R21AI156162-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Nara Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,166
- **Award type:** 1
- **Project period:** 2021-04-02 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108607

## Citation

> US National Institutes of Health, RePORTER application 10108607, To employ gamma-peptide nucleic acid oligomers to interfere with viral replication (1R21AI156162-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10108607. Licensed CC0.

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