# Engineered polymeric adjuvants for heart-redirected targeting and gene therapy

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $579,425

## Abstract

In this project, we aim to develop and improve the delivery of various therapies, including adeno-associated
viral (AAV) and nanoparticle (NP) gene therapy to the heart. The impetus for this project is a high unmet need
for cardiomyopathies that do not have current treatments. Cardiomyopathy is an umbrella term for disorders of
cardiac muscles. Collectively, these disorders are highly prevalent, and many lack specific treatment options.
Because most gene therapies are one-time, single-dose treatments, improving heart targeting becomes critical
to achieve adequate efficacy. Systemic delivery of AAV or NP vectors in adult, often overweight, patients is
fraught with challenges related to the low transduction of cardiomyocytes and the life-threatening immune
response. By enhancing the delivery of genetic information to the heart and reducing its sequestration by the
liver, we would be able to increase efficacy and improve safety of these therapeutics. Based on the discoveries
in our lab, we hypothesized that by co-delivering AAV, NPs, oligonucleotides, antibodies or other therapeutics
with an engineered polymeric adjuvant, a synthetic enhancer, will improve the therapeutic index of these
therapeutics. We also hypothesized that this technology that we call heart-redirected targeting (HRT) has a
potential to enhance the delivery of any therapeutic entity. This hypothesis is supported by the preliminary
studies on mechanism of action of HRT and examples of delivery of various therapeutic modalities. Therefore,
in this proposal, we aim to: 1) test the risk/benefit of HRT; 2) investigate the generality and reproducibility of the
HRT; 3) elucidate the mechanism of action of HRT in human-relevant cellular models; 4) test the long-term
efficacy of HRT with AAV carrying frataxin (FXN) transgene in genetic mouse model of Friedreich’s ataxia (FA).
In order to decrease mortality in FA, it is critical to treat cardiomyopathy, which is the dominant cause of death
among FA patients. If successful, this work will have an unprecedented impact on drug delivery and gene
therapy, because the HRT system is agnostic to the delivery vehicle, opening a possibility of cardiac targeting
with a wealth of approaches developed to date.

## Key facts

- **NIH application ID:** 10978027
- **Project number:** 1R01HL166241-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Andrei Maiseyeu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $579,425
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978027

## Citation

> US National Institutes of Health, RePORTER application 10978027, Engineered polymeric adjuvants for heart-redirected targeting and gene therapy (1R01HL166241-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978027. Licensed CC0.

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