06 August 2020
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.
- CRISPR is now being tested inside the body — for safety and effectiveness — to treat congenital blindness.
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.
Transcripts show George Floyd told police "I can't breathe" over 20 times
Section2Newly released transcripts of bodycam footage from the Minneapolis Police Department show that George Floyd told officers he could not breathe more than 20 times in the moments leading up to his death.
Why it matters: Floyd's killing sparked a national wave of Black Lives Matter protests and an ongoing reckoning over systemic racism in the United States. The transcripts "offer one the most thorough and dramatic accounts" before Floyd's death, The New York Times writes.
The state of play: The transcripts were released as former officer Thomas Lane seeks to have the charges that he aided in Floyd's death thrown out in court, per the Times. He is one of four officers who have been charged.
- The filings also include a 60-page transcript of an interview with Lane. He said he "felt maybe that something was going on" when asked if he believed that Floyd was having a medical emergency at the time.
What the transcripts say:
- Floyd told the officers he was claustrophobic as they tried to get him into the squad car.
- The transcripts also show Floyd saying, "Momma, I love you. Tell my kids I love them. I'm dead."
- Former officer Derek Chauvin, who had his knee on Floyd's neck for over eight minutes, told Floyd, "Then stop talking, stop yelling, it takes a heck of a lot of oxygen to talk."
Read the transcripts via DocumentCloud.