# Optical imaging in the development of molecularly targeted AAV for cardiac regeneration after myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $403,750

## Abstract

The overarching goal of this proposal is to engineer novel, multifunctional drug and gene delivery systems
that can target therapies to particular cells and intracellular compartments and also monitor delivery and
determine therapeutic efficacy through the integration of advanced imaging technologies. To pursue this goal,
this multi-PI application proposes to leverage existing strengths within UVA including: expertise in using
advanced biomedical imaging techniques to assess ischemic heart disease in animal models and re-engineering
recombinant adeno-associated vectors (rAAV) (French), screening molecular libraries in vivo to identify specific
peptides capable of targeting diseased tissue (Kelly) so that the capsid surface displays specific peptides
capable of targeting gene delivery to diseased tissue (Dasa). Not only will the targeting peptides validated during
this project be used to develop a novel AAV-based cardiac gene delivery system, future applications include
labeling the cardiotropic peptides with fluorophores and/or radiotracers to create contrast agents for the
molecular imaging of ischemic heart disease. Similarly, the same cardiotropic peptides may prove valuable in
targeting novel therapeutic agents directly to the heart after intravenous (iv) injection. In preliminary studies, the
two PIs have already demonstrated the robustness and utility of the interdisciplinary technologies needed to
achieve the following specific aims:
 1) Validate additional peptides specific for the infarct border zone by evaluating their specificity with
in vivo optical imaging and ex vivo confocal microscopy.
 2) Optimize the cardiac gene delivery system by grafting cardiotropic peptide ligands into the AAV9
capsid for the selective delivery of expression cassettes driven by a cardiac-specific promoter.
 3) Demonstrate the utility of the cardiac-targeted AAV gene delivery system by overexpressing the
TTK protein kinase and down-regulating Meis1 transcription factor in the heart after myocardial
infarction, then use advanced imaging techniques to quantify the therapeutic effect on LV remodeling.
 The development of this cardiac-targeted gene delivery system will establish a foundation for future research
efforts including the engineering and evaluation of cardiac-targeted nanoparticles and liposomes as
multifunctional platforms to facilitate not only the molecular imaging of ischemic heart disease, but also the
targeted delivery of novel small molecule therapies. This proposal takes a multidisciplinary approach that makes
extensive use of biomedical imaging, thus spanning the fields of radiology, cardiology, molecular imaging and
molecular virology. The combined research/development project will result in: a) new targeting peptides that
interact specifically with cardiomyocytes in vivo, b) new AAV-based systems for cardiac gene delivery with
considerable potential for both pre-clinical research and translation to clinical applications, c) insights into th...

## Key facts

- **NIH application ID:** 9903440
- **Project number:** 5R01HL147193-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Brent A French
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903440

## Citation

> US National Institutes of Health, RePORTER application 9903440, Optical imaging in the development of molecularly targeted AAV for cardiac regeneration after myocardial infarction (5R01HL147193-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903440. Licensed CC0.

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