CRISPR Technology Has Cured Patients of Certain Genetic Diseases, But Not All Patients Can Receive It Due to Cost, Accessibility

There are patients who have been cured of genetic diseases, such as sickle cell disease, thanks to CRISPR technology, explained Kevin Davies, PhD, executive editor of The CRISPR Journal and GEN Biotechnology and author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, Breakthrough: The Race for the Breast Cancer Gene, and Cracking the Genome, during the keynote address at the ACCC Annual Meeting & Cancer Center Business Summit in Washington, DC. Davies explained further that curing patients of certain genetic diseases is just the beginning of where CRISPR technology can go.¹

“CRISPR is truly, almost literally, a cutting-edge technology. The Nobel Prize Committee a few years ago called it ‘the genetic scissors.’ So that's about as cutting edge as you get,” Davies said during his presentation. “Just in the past decade, we can usher [CRISPR] into cells, deliver these molecular machines into the nucleus—into the command center of a cell—and then [let it] find its way and weave around all of that DNA that's coiled and bundled and packaged into 23 pairs of chromosomes, those 6 billion letters of genetic information—the A's, C's, T's, and G's—to find that 1 letter that is causing a serious genetic disease or potentially triggering a familial form of cancer. That's what CRISPR can do—and it's doing it—this isn't science fiction.”¹

Kevin Davies, PhD, executive editor of The CRISPR Journal and GEN Biotechnology, discusses the potential of CRISPR technology during the keynote address at the ACCC Annual Meeting & Cancer Center Business Summit in Washington, DC.

Davies explained further that in 2020, a paper was published in Science by lead author Edward A. Stadtmauer, MD, from the University of Pennsylvania, presenting the results of the first in-human phase 1 clinical trial using CRISPR-Cas9 gene-editing technology to enhance the natural ability of human T cells to fight cancer.^1,2 Davies noted that the conclusion from this paper is that CRISPR can be used as a precision tool to develop chimeric antigen receptor (CAR) T cells.¹

During the trial, the investigators deleted 2 genes encoding the endogenous T cell receptor (TCR) chains, TCRα (TRAC) and TCRβ (TRBC), in T cells to reduce TCR mispairing and enhance the expression of a synthetic, cancer-specific TCR transgene (NY-ESO-1). Additionally, they also removed a third gene encoding programmed cell death protein 1 (PD-1; PDCD1) to improve antitumor immunity. The results of the trial showed that immunogenicity was minimal under these conditions and that CRISPR gene editing for cancer immunotherapy was feasible.^1,2

“Okay, so that's good. Well, this is even better: A young woman in England named Alyssa [who is aged] 13, maybe 14 years,” Davies said. “She has received a form of this therapy called ‘base edited cells’ to treat a very incurable form of T-cell acute lymphoblastic leukemia, and she's currently at home recovering because this CAR T has worked better than any of her physicians thought it could possibly work.”¹

Davies noted that David R. Liu, PhD, and his team at the Broad Institute of MIT and Harvard have also developed a new version of CRISPR that still involves the use of enzymes. However, this new technology doesn’t use the enzymes as scissors, but instead as a sort of delivery system that has blunted those scissors and attached other enzymes to perform different types of chemistry.¹

“These enzymes can perform a much more delicate surgery, literally DNA surgery, on some of those A’s, C’s, T’s, and G's, to make, in some cases, a single letter change,” Davies said. “Two postdocs in this lab published within a year of each other 2 different flavors of base editing, both in Nature. One of them is now at a company called Beam Therapeutics, which is commercially developing these technologies. The results, as we just saw with Alyssa, have been demonstrated in preclinical models, and could potentially be on the way to the clinic for a number of different diseases.”¹

The current estimate is that approximately 200 patients have received or are currently receiving some form of CRISPR gene editing in clinical trials, explained Davies. However, a recent New York Times op-ed by Fyodor Urnov, PhD, a professor of molecular and cell biology at the University of California, Berkeley, and a gene editor at its Innovative Genomics Institute, discussed some ongoing concerns regarding whether the potential of CRISPR is going to reach all of the patients who need it.¹

“All of the patients with literally thousands of known, catalogued genetic diseases, could, in principle, be treated more or less today, if we had the infrastructure and the resources and the money to do it,” Davies said. “We must build a world with CRISPR for all, Urnov writes. One of the big problems, of course, is just cost. We are in an arms race, it seems, to develop the world's most expensive drug. It's like a badge of honor, ‘Look, our drug was $2.8 million US,’ or ‘Oh no—ours is $3.5 million US.’”¹

Views on the issue of cost will differ, depending on the interests of the stakeholder in question, according to Davies. For investors in these companies, the high cost is great; but for the patients, the vast majority cannot afford multi-million dollar accrued costs for therapies on the market for what have become curable diseases today.¹

“The companies will probably justify that by saying yes, but didn't you know, the actual lifetime cost of managing a sickle cell patient who can now live for many, many decades and have a normal healthy lifespan, could be $5 or $6 million [dollars]. So you see, we're saving the health care system money," Davies said. “I don't have an answer for that.”¹

Davies noted that beyond the concern of financial affordability and access, there remains exciting opportunities for CRISPR to continue to have an impact in medicine and on life on this planet. In a recent issue of Science, for example, authors highlighted a particular investigation into the use of pigs for xenotransplantation.¹

“Pigs turn out to be a fantastic facsimile for humans in terms of organ transplantation. But we have to ensure that their genomes are safe when transported into the human body. So CRISPR is being used by a company called eGenesis, co-founded by Luhan Yang, PhD, and George Church, PhD, to remove all of the potentially cancer-causing segments in the pig genome to make them potentially safe for xenotransplantation,” Davies said. “We've already seen some reports of this starting to take place.”¹

References

1. Davies K. Precision Medicine: Stories from the CRISPR Revolution. Presented at: ACCC Annual Meeting & Cancer Center Business Summit in Washington, DC; March 9, 2023.

2. Stadtmauer EA, Fraietta JA, Davis MM, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367(6481). doi:10.1126/science.aba7365