UCSF Awarded Nearly $8.4M for CRISPR_SCD001 Gene Editing Trial
The University of California, San Francisco (UCSF) has been awarded $8.39 million to fund a Phase 1/2 clinical trial of CRISPR_SCD001, the first non-viral and CRISPR-Cas9-based gene editing therapy for sickle cell disease (SCD).
Researchers will use the gene-editing technology to attempt to correct a genetic mutation in the blood stem cells of patients with severe SCD.
The grant comes from the California Institute for Regenerative Medicine or CIRM, which was created by the state’s residents to accelerate the process of getting stem cell treatments to patients.
CIRM previously funded CRISPR_SCD001’s preclinical development — including studies to secure the needed approval to conduct the first-in-human trial in the U.S. The National Heart, Lung, and Blood Institute (NHLBI) will conduct the trial along with UCSF.
This support is part of an agreement between CIRM and NHLBI to advance the development of gene therapy programs for SCD under the NHLBI’s “Cure Sickle Cell” initiative. Under that pact, the organizations aim to co-fund SCD gene therapy programs. This trial also will be eligible for co-funding by the NHLBI.
“We are pleased to fund a promising trial for sickle cell disease that uses the Nobel Prize winning gene editing technology CRISPR-Cas9,” Maria T. Millan, MD, CIRM’s president and CEO, said in a press release.
Adapted from a natural defense mechanism of bacteria, CRISPR-Cas9 allows researchers to edit parts of the genome — all genes that are present in people’s DNA — by adding, removing, or changing specific DNA sections.
“This clinical trial is a testament to how the CIRM model supports promising early-stage research, accelerates it through translational development, and advances it into the clinics,” Millan added.
SCD is caused by mutations in the HBB gene, which provides instructions to make the beta subunit of hemoglobin, a protein found in red blood cells that transports oxygen.
CRISPR_SCD001 uses the new CRISPR-Cas9 gene-editing tool to replace the mutated HBB gene with a healthy version in a patient’s blood cell precursors, also known as hematopoietic stem cells. These cells are first collected from a patient’s bone marrow, and then genetically modified in the lab using the gene-editing tool. The modified cells are then returned to the patient in the form of a stem cell transplant.
Notably, CRISPR-Cas9 machinery will be delivered to cells through electrical pulses that create temporary pores in their membranes. That’s in contrast to other experimental gene-editing approaches for SCD that rely on a virus as a transport agent.
By restoring the production of normal hemoglobin and preventing red blood cells from becoming damaged and acquiring a sickle-like shape, CRISPR_SCD001 is expected to be a potential curative approach for SCD.
The Phase 1/2 trial (NCT04774536), being conducted at UCSF’s Benioff Children’s Hospital Oakland and the University of California, Los Angeles, will mark the first attempt to correct the faulty HBB gene in a patient’s own cells with non-viral delivery of CRISPR-Cas9 gene-editing tools.
Led by Mark Walters, MD, a professor of pediatrics at UCSF and the director of the pediatric blood and marrow transplant program at Benioff, the study will evaluate the safety and effectiveness of a single dose of CRISPR_SCD001 in up to nine people, ages 12–35, with severe SCD.
If the therapy shows a favorable safety profile in the first six treated patients, all adults, three adolescents, ages 12–18, will be recruited to investigate its safety in younger patients.
The trial’s main goal is to assess the rate of side effects (adverse events) and serious adverse events among participants. As secondary and additional goals, the researchers will evaluate other safety measures, as well as changes in the rates of vaso-occlusive crises (VOCs) and other SCD-related complications. Levels of hemoglobin and markers of red blood cell destruction also will be examined.
In addition, the study will evaluate participants’ quality of life, lung and heart function, exercise capacity, and survival.
Along with the UCSF award, CIRM also granted $51.08 million to 15 community colleges and universities across California to fund programs that will help undergraduate and master students gain knowledge and experience in stem cell research.
“As the field advances, we must also meet the demand for promising young scientists,” Millan said, adding that these CIRM-funded programs “will provide students with the tools and resources to begin their careers in regenerative medicine.”