# Development of epidermal progenitor cell-based therapy for regenerative medicine

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $405,000

## Abstract

Project Summary
 Somatic gene therapy provides a promising therapeutic approach for treatment of a variety of otherwise
terminal or severely disabling diseases. The recent development of genome editing technology, including
CRISPR (clustered regularly-interspaced short palindromic repeats) system, has made it possible to perform
precise genetic engineering in cells. However, clinical application of CRISPR technology to human patients has
been challenging due to the inadequate efficacy in vivo using conventional delivery approach. Thus, it is
urgently needed to develop an ex vivo platform that can combine both precise genome editing in vitro with
effective application of engineered cells in vivo.
 The epidermal progenitor cells of skin have several unique advantages, making it particularly suited for
ex vivo gene therapy. Human skin is the largest and most accessible organ in the body, making it easy to isolate
skin epidermal progenitor cells and monitor the tissue for potential detrimental complications. Anatomically, skin
epidermis is separated from vasculature by the basement membrane, which prevents potential dissemination of
genetically modified cell in vivo, making the potential therapy tissue specific and safe. Lastly, the potential
applicability of cutaneous gene therapy is broad because it has been well documented that proteins expressed
in skin epidermal cells can cross the epidermal/dermal barrier and reach circulation to achieve therapeutic effect
in a systematic manner. In addition, ectopic expression of metabolic enzymes in skin epidermal cells can
transform the engineered skin into a “metabolic sink” for correction of various metabolic disorders. However,
despite the potential clinical importance, research in epidermal progenitor cell-based therapy (cutaneous gene
therapy) has been greatly hindered due to lack of an appropriate mouse model. Although mouse or human skin
can be transplanted to immunodeficient mice, lack of an intact immune system makes it impossible to examine
the potential outcomes and complications that the therapy may elicit in vivo. We have now resolved the
technical hurdle and established a unique mouse-to-mouse skin transplantation model that can stably introduce
genome-edited epidermal progenitor cells into immunocompetent mice. In this proposal, we will take advantage
of this novel platform and explore the feasibility and clinical potential of cutaneous gene therapy for treatment of
genetic diseases, including phenylketonuria (PKU) and hemophilia A. Together, our studies will establish a
unique and powerful model for cutaneous gene therapy with current genome editing technology, revealing the
therapeutic potential for somatic gene therapy with epidermal progenitor cells.

## Key facts

- **NIH application ID:** 9842019
- **Project number:** 5R01OD023700-04
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Xiaoyang Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2017-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842019

## Citation

> US National Institutes of Health, RePORTER application 9842019, Development of epidermal progenitor cell-based therapy for regenerative medicine (5R01OD023700-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842019. Licensed CC0.

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