UCSF Benioff Children's Hospital Oakland is enrolling patients in a groundbreaking clinical trial that seeks to cure sickle cell disease by targeting its genetic roots. The trial, leveraging CRISPR-Cas9 technology, offers a potential one-time treatment that corrects the disease-causing mutation without the need for donor stem cells.
Aims to Correct Genetic Mutation
Sickle cell disease, affecting approximately 100,000 Americans and millions worldwide, is caused by a single mutation in the beta-globin gene. This mutation leads to the production of defective hemoglobin, deforming red blood cells into a rigid, sickle shape. These misshapen cells can block blood flow, causing severe pain, organ damage, and a significantly shortened lifespan, disproportionately impacting the Black community.
The clinical trial aims to rewrite the narrative for patients by using CRISPR-Cas9 to directly correct the genetic mutation. The process involves extracting blood stem cells from the patient, editing out the mutation, and reinfusing 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.
Precision Medicine in Action with CRISPR-SCD001
The trial utilizes 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.
"The use of CRISPR gene editing to fix the sickle cell disease-causing mutation in each patient's own blood-forming stem cells required the development of new methods to produce more than 100 million cells per patient that are gene-corrected, healthy and pure," said Donald Kohn, MD, a distinguished professor of microbiology, immunology and molecular genetics and of pediatrics at UCLA.
The trial is beginning with up to six adult patients in California, with safety evaluations performed 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.
Years of Collaborative Effort
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 started from a conversation I had with Mark Walters around 10 years ago, so it's gratifying to see it advance to a clinical trial," said Doudna, PhD, the Li Ka Shing Chancellor's Chair in Biomedical and Health Sciences at UC Berkeley. "I'm hopeful for a future with more affordable, accessible, and safer cures for sickle cell disease, and this is an important step in that direction."
