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, told me in an interview.
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 other diseases (like Ebola and dengue), 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.
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 the pathogen is found, enzymes guided by the CRISPR sequence put out a signal.
- CRISPR can also lead enzymes to 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.
- But there are concerns about off-target editing and unknown long-term effects of gene editing, and challenges with getting the sizable CRISPR system through the membranes and to the DNA of the cells that need editing.
- Last month, Doudna's team reported finding a compact form of CRISPR that she suspects may be easier to get it into cells, potentially driving the cost of therapies down.
- That's "the bleeding edge" of the field, says Doudna.
The intrigue: CRISPR could one day be wielded in future pandemics.
- It might become possible to edit immune cells in the body so they are less susceptible to becoming exhausted by a disease, says Doudna.
- Or CRISPR could be used to program immune cells to recognize regions of a type of virus and be ready for a pathogen before it shows up, she says, pointing to the use of CRISPR to prime the immune system to attack cancer.
Read the entire interview.