CRISPR genome editing technology, which was developed at UC Berkeley, has been approved for clinical trials to correct gene mutations responsible for sickle cell disease.
Sickle cell disease has been an “early target” for gene therapy because it is caused by a single-letter DNA mutation, according to campus Innovative Genomics Institute, or IGI, spokesperson Andy Murdock. He added that this makes the gene-editing process “theoretically straightforward.”
“It’s the most common hereditary disease worldwide, disproportionately affecting the Black population in the US,” Murdock said in an email. “It has a long history of being unjustly overlooked and understudied.”
Two years after discovering CRISPR in 2012, campus biochemist Jennifer Doudna first approached IGI and the Children’s Hospital Oakland Research Institute to work towards sickle cell gene therapy.
The process essentially consists of first cutting the DNA of stem cells, then supplying a synthetic piece of DNA with the proper nucleotide to correct the mutation, according to UCLA professor Donald Kohn, who will lead clinical trials at UCLA and work with UCSF professor of pediatrics Mark Walters. After freezing and eliminating uncorrected stem cells, they hope to see patients making red blood cells with the normal protein.
“There has been a lot of excitement about the promise of the technology for curing genetic diseases that haven’t been well addressed,” Murdock said in the email. “Compared to how long it typically takes to produce new medicines, the amount of progress in under 10 years is quite amazing.”
The trials will take place over the next four years.
The researchers aim to treat nine individuals, starting with six adults and then moving to adolescents, according to Fyodor Urnov, campus molecular and cell biology professor and IGI director of technology and translation.
“The first rule of medicine is ‘do no harm.’ I mentioned that sickle is a tragic disease — we have to be careful and patient safety is our paramount concern,” Urnov said. “It would be overwhelmingly unethical to proceed faster.”
Urnov added that in addition to safety, the researchers will focus on the efficacy of gene therapy. If successful, they will discuss a pivotal trial to treat a larger group of individuals with the U.S. Food and Drug Administration.
Urnov said in the long run, as a nonprofit, the IGI’s aspirational goal is to reduce the cost of treatment from $2 million to below $100,000 so that it can be distributed differently from something that would be commercially delivered.
“Maybe this becomes a federal effort,” Urnov said. “To the extent that the United States of America should have a vision for a national program that ultimately is not driven by the commercial sector to address an unmet medical need, I would argue that sickle cell disease very much rises to that.”