# Bioengineering Strategies for Cardiovascular Disease

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $769,399

## Abstract

PROJECT SUMMARY
Vascular disease is common and deadly for millions of Americans. Current medical
therapies for vascular disease are limited and are associated with significant morbidity
and mortality. Therefore, vascular diseases warrant new and novel therapies. The long
range goal and the clinical significance of this proposal are to use our newly
developed ETV2 knockout pigs as hosts ultimately for the production of personalized
human vasculature for clinical applications. The goal of this current revised application
is to establish a nonhuman primate platform in a pig that would provide the feasibility for
engineering humanized vasculature in a gene edited pig. Our laboratory discovered
Etv2 as a downstream target of Nkx2-5 and defined that Etv2 mutant mouse embryos
were nonviable and lacked endothelial/vascular and hematopoietic lineages. Using
CRISPR/Cas9 gene editing technology, we have further established that ETV2 mutant
porcine embryos lack vascular and blood lineages. Based on our results, our overall
hypothesis is that Etv2 is an essential factor for the master molecular program for
vascular lineages during development. In these proposed studies, we will utilize a
number of emerging technologies to engineer a paradigm shifting nonhuman primate
vasculature in a genetically modified animal surrogate. To examine our hypotheses, we
will address the following specific aims: Specific Aim #1: To define the capacity of
blastocyst complementation, using GFP labeled porcine blastomeres, to fully
rescue the ETV2 null porcine host; Specific Aim #2: To define the capacity of
nonhuman primate stem cell populations for porcine blastocyst complementation
and Specific Aim #3: To engineer nonhuman primate vasculature in the ETV2
mutant porcine host. In these studies, we will use state-of-the-art gene technologies
and macaque GFP-labeled stem cell populations to engineer a nonhuman primate
vasculature in a large animal model. This nonhuman primate large animal model will be
an important resource for regenerative medicine and will serve as a platform for
generating personalized humanized porcine models. This strategy has the capacity to
have a profound impact on the development of emerging therapies for chronic vascular
diseases and transplantation. Given the tremendous morbidity and mortality of
cardiovascular disease in our society, this proposal could have important clinical impact.

## Key facts

- **NIH application ID:** 9985220
- **Project number:** 5R01HL144582-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Daniel J. Garry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $769,399
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985220

## Citation

> US National Institutes of Health, RePORTER application 9985220, Bioengineering Strategies for Cardiovascular Disease (5R01HL144582-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985220. Licensed CC0.

---

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