Jan 8, 2018

CRISPR may not work in some people

Illustration: Rebecca Zisser / Axios

CRISPR, the precision gene-editing technology researchers hope can be used to treat genetic illnesses, may be ineffective or even dangerous for a large subset of humans, according to STAT news. A new paper reports many people may be immune to the two most commonly used types of CRISPR. However, some scientists told STAT it may be possible to work around this problem.

Why it matters: We're moving closer to using CRISPR in human trials, but if the results of this paper are confirmed (it hasn't been peer reviewed yet) it's possible the treatment could be stopped by the immune system, or worse, trigger a dangerous inflammatory immune response.

The background: CRISPR is a suite of genes that bacteria use as an immune system to fight viruses. The genes can cut and splice parts of a bacteria's genome — and, in the lab, human genomes. Other parts of the CRISPR suite might be used to edit RNA, create cellular recorders, diagnose diseases or to kill bacteria without antibiotics.

What they found: Since CRISPR comes from bacteria, it makes sense that our body's immune systems would recognize and attack it, and the bacteria we've taken CRISPR from are some of the most common ones humans encounter.

  • 65% of people have immune proteins for the CRISPR Cas9 genome that comes from the bacteria Staphylococcus pyogenes (strep throat), and 75% are immune to CRISPR that comes from Staphylococcus aureus (staph infections), the two most common types of CRISPR.
  • Immune cells in about half of the people studied targeted CRISPR from S. aureus. It's unknown if other parts of the CRISPR suite besides Cas9 would be affected.

Yes, but this doesn't spell the end of CRISPR. "“At the end of the day, I’m not that concerned about it,” Daniel Anderson of the Massachusetts Institute of Technology, tells STAT. “But we want to do some experiments to learn more.”

There are workarounds: Currently, many CRISPR proposals involve editing a person's cells outside of the body, and then adding the cells back in, thus circumventing the immune system. It's possible that other CRISPR proteins won't be detected by the human body.

Proceed with caution: Study author Matthew Porteus of Stanford told STAT the field can't afford a death, noting the 1999 death of a man in a gene therapy trial, who was thought to have died from an immune response. "I would hate to see the field have a major setback because we didn’t address this potential issue,” Porteus said.

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