# Targeted Systemic Delivery of SDF-1 DNA for the Treatment of Chronic Heart Disease

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2021 · $471,464

## Abstract

PROJECT SUMMARY / ABSTRACT
Stromal-derived factor-1 (SDF-1)-based gene therapy that can improve mesenchymal stem cell (MSC) homing
to the region of myocardial infarct for the treatment of acute myocardial infarction (MI) or chronic heart failure
(CHF) has shown considerable promise in preclinical and clinical trials. However, the most established
technology requires trans-endocardial injection using a specific device, which can only be handled by an
expert. For convenience administration and cost-effective treatment, a targeted systemic delivery strategy has
to be developed. In this application, a plasmid DNA encoding SDF-1 will be systemically and specifically
delivered to the infarct site by the formation of the SDF-1/ischemic myocardium targeting peptide (IMTP)
complex. To generate the SDF-1/IMTP complex, for the first time, we utilize the ligand-to-metal charge transfer
transition allowing for direct incorporation of the targeting peptide to the plasmid SDF-1 DNA without the need
for any gene carriers. We hypothesized that the LMCT transition between Zn2+ ions and the sulfhydryl group in
cysteine of the targeting peptide could spontaneously drive the integration of the peptide to the plasmid SDF-1
that has already been modified to contain Zn2+ ions. It has been known that divalent metal ions, such as Zn2+,
lead to the conversion of normal B-DNA to metal-bound DNA (M-DNA) through intercalation into the DNA base
pairs in the pH range of 7.0-8.5. In the preliminary studies, we generated M-DNA using Zn2+ ions, confirmed
the formation of the M-DNA/targeting peptide complex through the LMCT transition, and demonstrated that the
M-DNA/targeting peptide complex led to the enhancement in the gene transfection in the target cells. In this
project, in an animal model of CHF, we intend to demonstrate therapeutic efficacy of the targeted systemic
delivery of a plasmid SDF-1 DNA by the formation of the SDF-1/IMTP complex generated through the LMCT
transition. To achieve the final goal, we intend to demonstrate the followings: 1) direct integration of IMTP into
the SDF-1 plasmid through the LMCT transition; 2) targeted transfection of the SDF-1 gene into hypoxic
primary cardiomyocytes and the infarct site in the animal model; and 3) facilitated migration of MSCs towards
the SDF-1 gradient in the animal model.

## Key facts

- **NIH application ID:** 10220114
- **Project number:** 5R01HL138242-06
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** YOUNG-WOOK WON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $471,464
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220114

## Citation

> US National Institutes of Health, RePORTER application 10220114, Targeted Systemic Delivery of SDF-1 DNA for the Treatment of Chronic Heart Disease (5R01HL138242-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220114. Licensed CC0.

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