One of the most well-known versions of the gene-editing tool CRISPR may not work in a large proportion of the population, according to recent research out of Stanford University in California.
CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene-editing technology that enables scientists to edit an organism's DNA. Many scientists consider the CRISPR-Cas9 system — which creates modified RNA segments that bind to the CRISPR-associated protein 9 enzyme — to be one of the most precise and least expensive gene-editing techniques currently in use.
However, a research paper released on BioRxiv, an archive of unpublished science papers, raises concerns about a common human immune response that might render CRISPR-based therapies ineffective.
Here are five things to know about the research findings.
1. A team of researchers from Stanford University assessed human immune responses to two types of Cas9 proteins used in CRISPR technologies, SaCas9 and SpCas9. They determined 79 percent of donors maintained antibodies against SaCas9 and 65 percent had antibodies against SpCas9, based on blood samples from 22 newborns and 12 adults. The researchers also found T-cells that target SaCas9 in 46 percent of donors.
2. These findings suggest patients with existing immune responses to Cas9 proteins might be immune to CRISPR-based therapies. However, Matthew Porteus, MD, PhD, senior author on the research paper, told STAT the findings should not hinder future CRISPR efforts, since much is left to discern regarding a patient's reaction to CRISPR technologies, such as how severe an immune response would be.
3. Dr. Porteus is working to develop a CRISPR-based therapy for sickle cell disease and is one of the scientific founders of Zug, Switzerland-based biotechnology company CRISPR Therapeutics. "Like any new technology, you want to identify potential problems and engineer solutions for them," Dr. Porteus told STAT. "And I think that’s where we're at."
4. Samarth Kulkarni, CEO of CRISPR Therapeutics, acknowledged the research paper's Jan. 5 release on bioRxiv resulted in a drop in the company's stock prices, according to the Boston Globe. However, he brushed aside concerns of CRISPR being ineffective, noting the research paper's findings had been presented at conferences in 2016. He added immune responses to CRISPR technology would likely be limited in regards to patient health.
"The data are not new," he told the Boston Globe. "What's new is that someone in the press picked it up and sensationalized it, and all of a sudden everyone else picked it up."
5. Other experts have expressed that the immune response highlighted in the research paper could be worked around. For example, many clinical trials being discussed involve removing cells from a patient and deploying a CRISPR-based therapy before returning the cells to the participant, according to STAT. In this scenario, there may be too few CRISPR proteins remaining in the patient's cells for their immune system to detect.