Editing the Code: UCSF's Mission to Cure Sickle Cell Disease with CRISPR
A new era of gene therapy has arrived for sickle cell disease, with UCSF leading the way toward one-time, potentially curative treatments for patients.
Sickle cell disease is a genetic blood disorder that deforms red blood cells, causing blockages that can lead to debilitating pain, organ failure, and a shortened lifespan. Affecting 100,000 Americans and the Black community disproportionately, the disease's impact goes beyond physical suffering; severe, lasting pain crises can stall careers and futures, showing the urgent need for a cure.
While several transformative therapies now exist, a new clinical trial, part of a University of California research consortium led by UCSF with UCLA and UC Berkeley’s Innovative Genomics Institute (IGI), is the first to directly correct the single-letter mutation that causes the disease at its genetic source. The goal is to bring this therapy to younger patients and correct the disease before it can cause irreversible organ damage.
This landmark trial, led by Mark Walters, MD, a professor of pediatrics at UCSF, has now enrolled its first patients at UCSF Benioff Children’s Hospital Oakland, marking a critical milestone in the journey from the lab to the clinic.
How Gene Correction Differs from Other Therapies
UCSF offers the two currently FDA-approved gene therapies, LYFGENIA and CASGEVY, which provide lasting, life-changing treatments by compensating for the effects of the mutated gene. These therapies are highly effective but currently limited to specific types of the disease, and a small percentage of patients still experience significant pain after treatment.
The new trial takes the next logical step, using a "gene correction" strategy to directly repair the mutation. The process involves taking a patient’s own blood stem cells and using a non-viral CRISPR-Cas9 platform to precisely edit them. These corrected, healthy cells are then returned to the patient via a bone marrow transplant.
“All of these gene therapies remove the need to search for an eligible donor, but our current CRISPR trial aims to remove the mutation sufficient for a life free of sickle cell disease,” says Walters.
First Participants Enrolled
The UCSF gene correction trial has now officially launched, with the first two participants enrolled as of August 2025. This marks the start of a carefully planned journey for each patient, designed to ensure the utmost safety.
The two patients will now begin months of preparation, including transfusions and the collection of their own stem cells, before the four-month cell manufacturing process begins at UCLA’s Human Gene and Cell Therapy Facility.
"We are thrilled to have our first participants enrolled," says Walters. "The journey is a long and careful one, but this rigorous approach is essential to giving this groundbreaking therapy the best possible chance of success."
Looking Ahead: From Adults to Adolescents
The next major milestone for the trial will be the infusion of the first patient’s edited cells, expected in early 2026. The results from these initial adult patients will be critical, as a key goal is to expand eligibility to younger patients.
"A critical next step after the initial safety evaluation in adults will be to enroll adolescents," says Walters. "We want to intervene as early as possible, as a one-time cure in a young person could prevent a lifetime of debilitating pain and organ damage. That is the future we are working toward."
This trial represents a significant milestone of hope for those with sickle cell disease. By pioneering the next generation of cures and delivering today's best therapies, UCSF’s Division of Pediatric Hematology is working to create a lasting impact, with the ultimate goal of giving every child with this disease the chance to build a future free from its burden.
Learn more about how we’re transforming care for patients with sickle cell disease at the UCSF Sickle Cell Center of Excellence.