SAN JOSE, Calif. – A team of scientists has used a powerful new gene-editing technique to fix the mutation that causes sickle cell disease, a key step toward a cure for the deadly immune system disease.
While more work is required before it is offered to patients, the researchers – from the University of California, Berkeley, UC San Francisco’s Benioff Children’s Hospital in Oakland and the University of Utah – have corrected the gene in enough cells to improve health.
“We’re very excited about the promise of this technology,” said senior researcher Jacob Corn, scientific director of the Innovative Genomics Initiative at UC Berkeley, in a prepared statement. “We’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”
It is part of an accelerating research movement made possible using the new technique, called CRISPR-Cas9, which acts as a microscopic scalpel and performs genomic surgery with a precision, efficiency and affordability once thought unimaginable.
Until the creation of CRISPR-Cas9, gene therapy was crude, laborious and unsafe for human use.
Similar efforts are underway at Stanford’s School of Medicine, led by Dr. Matthew Porteus. Using the campus’ first cell manufacturing plant, the Stanford team aims to start human trials in 2018. They are targeting sickle cell anemia and also beta thalassemia, two diseases that ravage the immune system.
Meanwhile, scientists at Duke University and two other independent labs are using this same approach to fix a muscle gene, restoring function in mice with an incurable type of muscular dystrophy.
Boston researchers are using the tool to treat a rare inherited eye disease that can cause blindness. Other teams are working to fix the genes that cause Huntington’s disease, Sanfilippo syndrome and cystic fibrosis.
More than 10,000 human diseases are caused by a single gene defect, according to Dr. Maria Grazia Roncarolo, co-director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.
The UC Berkeley and UCSF team used CRISPR-Cas9 to correct the disease-causing mutation in hematopoietic stem cells – the young cells that mature into red blood cells – isolated from blood of sickle cell patients.
They excised the bad gene, using CRISPR. Then they introduced a good gene. The corrected cells produced healthy hemoglobin, which mutated cells do not make at all.
Future work will require additional lab research, expanded testing in mice and a rigorous analysis of its safety, the researchers said. The results were reported in the online journal Science Translational Medicine.
“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Corn said in a prepared statement. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”