# In Vivo Hematopoietic Stem Cell Gene Therapy of Beta-Thalassemia and Sickle Cell Disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $657,943

## Abstract

Abstract:
Hematopoietic stem cell (HSC) gene therapy could provide a curative treatment for a number of blood diseases.
The conventional approach is based on ex vivo HSC gene transfer and has achieved encouraging results.
However, the high cost and side effects limit the patient accessibility of ex vivo HSC gene therapy. We have
developed an in vivo HSC transduction approach involving HSC mobilization and intravenous viral vector
injection. The approach is highlighted by its relatively low cost and technical simplicity. It could be provided as
an outpatient treatment. We have demonstrated its safety and efficacy in several murine disease models,
including β-thalassemia, Sickle Cell Anemia, and hemophilia A, and more recently, in rhesus macaques. With
more gene therapy products on the horizon, the application of in vivo HSC transduction could extrapolate genetic
treatments to a larger patient population. Further improvements of in vivo HSC gene therapy on the road to
clinical application include more effective mobilization protocols, complete elimination of innate responses upon
intravenous vector injection, more advanced virus capsid modifications that circumvent pre-existing anti-vector
immunity, improved in vivo selection regimens, as well as new methods for purification of gene transfer vectors.
In this application, we will successively test hypotheses to improve in vivo HSC gene therapy approaches for
thalassemia and Sickle Cell Disease in mouse models. We will then validate the best combination of
improvements in hon-human primates. Safety, efficacy, portability, and low costs are the major driving forces in
the design/optimization of each technological unit.

## Key facts

- **NIH application ID:** 10205378
- **Project number:** 2R01HL130040-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ANDRE Michael LIEBER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $657,943
- **Award type:** 2
- **Project period:** 2016-06-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205378

## Citation

> US National Institutes of Health, RePORTER application 10205378, In Vivo Hematopoietic Stem Cell Gene Therapy of Beta-Thalassemia and Sickle Cell Disease (2R01HL130040-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10205378. Licensed CC0.

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