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CRISPR co-discoverer: How gene editing could help fight future pandemics

The coronavirus pandemic is accelerating the development of CRISPR-based tests for detecting disease — and highlighting how gene-editing tools might one day fight pandemics, one of its discoverers, Jennifer Doudna, tells Axios.

Why it matters: Testing shortages and backlogs underscore a need for improved mass testing for COVID-19. Diagnostic tests based on CRISPR — which Doudna and colleagues identified in 2012, ushering in the"CRISPR revolution" in genome editing —are being developed for dengue, Zika and other diseases, but a global pandemic is a proving ground for these tools that hold promise for speed and lower costs.

Driving the news: Last week, the NIH awarded $250 million for the development of COVID-19 diagnostic tests to a handful of companies, including Mammoth Biosciences, which is working on a CRISPR-based test that CEO Trevor Martin says will deliver 200 tests per hour per machine.

  • Another CRISPR-based test, developed by Sherlock Biosciences and CRISPR pioneer Feng Zhang, received an emergency use authorization (EUA) from the Food and Drug Administration in May — the agency's first for any CRISPR-based technology. (Mammoth has since received an EUA for another CRISPR-based test.)
  • "In a way, the timing of the pandemic coincided with this technology being ready to address this emerging need," says Doudna, a co-founder of Mammoth and a biochemist at UC Berkeley.
  • Of note: UC Berkeley and The Broad Institute of MIT and Harvard, where Zhang is a professor, are in a years-long patent battle over the use of CRISPR in human cells, with potentially billions of dollars from licensing the technology at stake.

The challenge now is "getting it into a format where it can be used easily either in a laboratory or at the point-of-care," like the doctor's office or home, she says.

How it works: Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR, are sequences of genetic code that bacteria naturally use to find and destroy viruses.

  • Diagnostic tests work by programming CRISPR to search for a particular stretch of RNA or DNA in a virus. If thepathogen is found, enzymes guided by the CRISPR sequence put out a signal.
  • CRISPR can also lead enzymesto a gene that the enzyme then precisely snips or edits, turning it on or off or changing its function.

That editing ability is viewed as having vast potential for treating disease, a nascent use of CRISPR.

  • Earlier this summer, researchers announced that a CRISPR-based therapy appeared to be effective in treating a woman with sickle cell anemia, NPR reported.
  • The approach, in which cells are removed from the body, edited and reinfused via a bone marrow transplant, is expensive. (Gene therapy for a related blood disorder costs about $1.8 million for the treatment alone.)
  • Efficiently delivering CRISPR directly to cells in the body could drive down the cost, says Doudna.

But there's a persistent problem: Getting the sizable CRISPR system through the membranes and to the DNA of the cells that need editing.

  • That's "the bleeding edge" of the field, says Doudna, whose team and others are trying to solve the delivery challenges.
  • Last month, they reported finding a compact form of CRISPR in a virus that infects bacteria. Doudna suspects its small size may make it easier to get it into cells.

And, there are other concerns about off-target editing with currently available enzymes and unknown long-term effects of gene editing directly in the body.

The intrigue: CRISPR could one day be wielded in future pandemics.

  • Some researchers propose it could be used to attack viruses like SARS-CoV-2.
  • Orit might be possible to one day edit immune cells in the body so they are less susceptible to becoming exhausted by a disease, Doudna says.

Yes, but: That would require sophisticated understanding of how a virus changes and the immune system's complex response to it.

  • Some of those questions could be unraveled using machine learning to determine the consequences of perturbing a particular gene in a specific tissue, Doudna says.
  • And if researchers can determine which regions of genetic material in a virus or bacteria don't change over time, CRISPR could be used to program immune cells to recognize those regions and be ready for a type of virus before it shows up, she says, pointing to the use of CRISPR to prime the immune system to attack cancer.

The big picture: Such "genetic vaccination" is a long way off, but it could eliminate having to wait until a virus shows up, make a vaccine to that virus and then vaccinate people, she says.

  • Each year, the influenza vaccine's makeup involves anticipating which strains may be most prevalent by studying the virus' proteins.
  • "I sort of imagine a day we could do that at the genetic level," Doudna says.

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