For decades, sickle cell disease has been a relentless adversary, causing untold pain and shortened lifespans for millions worldwide. Now, a groundbreaking clinical trial at UCSF Benioff Children's Hospital Oakland is rewriting the story. Leveraging the revolutionary precision of CRISPR-Cas9 technology, this trial offers not just treatment but the possibility of a cure—one that addresses the disease at its genetic roots without the need for donor stem cells.

A Revolutionary Approach to Sickle Cell Disease

Sickle cell disease is caused by a single mutation in the beta-globin gene, leading to the production of defective hemoglobin that deforms red blood cells into a rigid, “sickle” shape. These misshapen cells can block blood flow, causing severe pain, organ damage, and dramatically reducing lifespan. Affecting approximately 100,000 Americans and millions globally, sickle cell disproportionately impacts the Black community.

In this new trial, researchers aim to rewrite the narrative for patients. Using CRISPR-Cas9, the team extracts blood stem cells from the patient, edits out the mutation, and reinfuses the corrected cells back into the body via a bone marrow transplant. The hope is that these edited stem cells will establish a healthy blood system free from sickle cell disease.

“This therapy eliminates the need for a donor while correcting the mutation at its source, offering a life free of sickle cell complications,” says Dr. Mark Walters, the trial’s principal investigator and a professor of pediatrics at UCSF.

Precision Medicine in Action

The trial’s innovative approach includes using CRISPR_SCD001, a patient-specific blood stem cell product engineered by a UC consortium. After extraction, the stem cells are sent to UCLA's Human Gene and Cell Therapy Facility, where they undergo a precise editing process. Electrical pulses create temporary pores in the cells, allowing the CRISPR-Cas9 tool to enter and repair the sickle cell mutation.

Dr. Donald Kohn, a leading expert in pediatric gene therapy at UCLA, underscores the technical leap involved: “We’ve scaled up production to generate more than 100 million gene-corrected cells per patient—an achievement that far surpasses earlier efforts.”

The trial is beginning with six adult patients, with safety evaluations after the first three treatments. If successful, the trial will expand to include adolescents aged 12 to 17. Researchers plan to follow participants for up to 15 years to assess long-term outcomes.

A Collaboration Decades in the Making

This trial represents the culmination of years of collaborative effort between UCSF, UCLA, and the Innovative Genomics Institute (IGI), a UC Berkeley-UCSF partnership founded by CRISPR pioneer and Nobel Laureate Jennifer Doudna. IGI developed the CRISPR technology, while UCLA contributed expertise in genetic analysis and cell manufacturing. UCSF Benioff Children's Oakland, with decades of experience in sickle cell care and gene therapy, leads the clinical application.

“The concept for this therapy began in a conversation I had with Mark Walters a decade ago,” reflects Doudna. “Seeing it reach clinical trials is deeply gratifying, and it’s a hopeful step toward more accessible and safer cures for sickle cell disease.”

This trial stands as a testament to the power of innovation and collaboration, offering a potential paradigm shift in treating one of the world’s most challenging genetic diseases.