# Site-Specific Correction of Sickle Cell Disease Using Acoustofludic Gene Delivery

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $32,340

## Abstract

Project Summary
Sickle cell disease (SCD) is among the most common monogenetic inherited disorders. Clinical
management of SCD is primarily supportive. However, in the most severe cases, the only definitive
curative option for patients suffering from SCD is an allogeneically matched hematopoietic stem cell
transplant. This hemoglobinopathy directly affects the structure and function of hemoglobin, leading to
deficiencies of β-globin chains in the development of functional adult hemoglobin. Furthermore, the
lack of fully matched donors for patients to receive a stem cell transplant runs the risk of adverse
immunogenic reactions, such as auto-immune disorders or graft-versus-host disease. Recent efforts to
address this disease and its clinical sequela have focused on gene therapies based on the
transplantation of autologous gene-modified hematopoietic stem & progenitor cells (HSPC), where a
patient's own cells are corrected and reinfused to enable production of fully functioning erythrocytes.
However, non-viral strategies for the batch processing of stem cell gene therapies are known to be
inefficient and are unable to meet clinical demands. We hypothesize that the optimization of an
acoustofluidic therapeutic platform that physically permeabilizes cells for the delivery of
CRISPR-Cas9 biomolecules will address this technologic gap. This high-throughput gene-delivery
strategy will enable our long-term goal to generate gene-modified stem cell therapies quickly and
efficiently for curing sickle cell disease. This physical permeabilization process renders target cells
transiently permeable, enabling vector uptake while minimizing damage to the cell membrane and
maintaining high levels of viability. In order to achieve our clinical target, our proposed specific
aims include: 1) optimize acoustofluidic gene delivery in model cell lines harboring the sickle
cell mutation and 2) evaluate site-specific correction of the sickle cell disease mutation in
hematopoietic stem and progenitor cells. Given the utility of this acoustofluidic technology, there is
a wide range of heart, lung, and blood disorders that can be addressed, overcoming the state of the art
for gene delivery. We expect the generation of rapid and safe gene-modified stem cell therapies using
our acoustofludic technology will greatly improve access to these medical interventions and the quality
of life for patients with the most severe cases of SCD.

## Key facts

- **NIH application ID:** 10023174
- **Project number:** 5F31HL149356-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jason Nathaniel Belling
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,340
- **Award type:** 5
- **Project period:** 2019-09-16 → 2021-06-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023174

## Citation

> US National Institutes of Health, RePORTER application 10023174, Site-Specific Correction of Sickle Cell Disease Using Acoustofludic Gene Delivery (5F31HL149356-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10023174. Licensed CC0.

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