# Developing a Temporally-Regulated Gene Therapy for Therapeutic Angiogenesis

> **NIH NIH F32** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $67,174

## Abstract

Project Summary/Abstract
Cardiovascular diseases affect millions of patients worldwide and account for nearly a third of deaths globally.
Ischemia, or a reduced blood supply, occurs in many cardiovascular diseases and is a pressing health challenge.
While current treatments primarily focus on re-vascularization of existing blood vessels, a significant sub-
population of patients are unable to tolerate the associated surgical procedures due to existing comorbidities.
Thus, there is great interest in developing strategies for therapeutic angiogenesis, which seeks to stimulate new
vascularization at the ischemic site. While many gene and cell therapies for therapeutic angiogenesis have been
tested in clinical trials, a clear benefit for patients remains to be seen. To date, most gene therapies deliver one
or two genes to the ischemic site, while cell therapies deliver progenitor or stem cells to produce paracrine factors
and self-organize into vasculature. A central limitation of these therapies is the inability to control the
temporal presentation of the expressed genes or secreted factors. Angiogenesis is a complex and
temporally regulated process, in which angiogenic factors first initiate the formation of a primitive vascular
network before maturation factors promote mural cell recruit and vessel stabilization. While studies with growth
factors suggest that sequential delivery of angiogenic and maturation factors is beneficial for establishing
functional vasculature, how the timing of the angiogenic-to-maturation transition impacts the functionality of the
established vasculature is unknown. How tissues naturally sense the correct timing for the angiogenic-to-
maturation transition is also unclear, but incorporating a sensor to regulate the expression of angiogenic and
maturation genes would be beneficial for creating a gene therapy with controlled dosing and minimal off-target
effects. In this proposal, synthetic biology tools will be combined with engineered models of vascularization and
an in vivo model of hindlimb ischemia to evaluate how the timing of angiogenic and maturation gene expression
impacts functional vascular network formation and recovery from ischemia. In Aim 1, a two-channel genetic
switch will be used to establish the relationship between the timing of the angiogenic-to-maturation transition and
vascular network functionality. In Aim 2, hypoxia response elements will be used to generate a hypoxia-regulated
genetic switch to control the induction of angiogenic and maturation genes. The genetic switch will be evaluated
for its ability to rescue perfusion in an in vivo hindlimb ischemia model. The associated training plan will prepare
the fellow for an academic career by enabling the fellow to obtain new skillsets in synthetic biology and in vivo
models. The fellow will have many opportunities for professional development through mentoring, networking,
attending conferences, and experience with grant writing. The fellow will tra...

## Key facts

- **NIH application ID:** 10535141
- **Project number:** 1F32HL165691-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Mai Ngo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535141

## Citation

> US National Institutes of Health, RePORTER application 10535141, Developing a Temporally-Regulated Gene Therapy for Therapeutic Angiogenesis (1F32HL165691-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10535141. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*