Talking Science with Dr. Chris Mason and Dr. Feng Zhang
Since the beginning of the pandemic, Vallee Scholars Chris Mason, PhD, Associate Professor at Weill Cornell Medicine, and Feng Zhang, PhD, James and Patricia Poitras Professor at MIT and Core Member of the Broad Institute, have been working separately and in collaboration on new COVID-19 tests. On a recent call with them both, Dr Mason talked about a 30-minute test he and his colleagues at Weill Cornell Medicine have put together using LAMP – loop mediated isothermal amplification – “basically a cousin of PCR, where the primers, which serve as Velcro strips that stick onto the virus and give you an anchor point, allow you to amplify that target and make many more copies at an exponential speed. We didn’t invent this chemistry – it’s been around for 20 years – we just started to try different primers to target the virus, got multiple primers working in the same reaction, and then optimized it slightly. Once we got it to work, we started to scale it up for lots of clinical samples coming to New York, as well as sequencing samples, and telling anyone and everyone we possibly could – making everything open source and public – to address the challenge of the pandemic. Now everyone is sharing methods and ideas as fast as possible to address that challenge.”
Dr Mason was talking from the lab of Dr Alison Kriegel, a physiologist at the Medical College of Wisconsin and an RNA specialist. When his brother, mayor of the town of Racine, Wisconsin, asked him for help with COVID testing, Dr Mason rang Dr Kriegel. They have since been collaborating on a COVID study with the Racine firefighters. This fast and efficient test uses saliva, which the firefighters have been trained to sample and process in a small machine. With the change of color of the flashing lights, they can tell whether the virus is present or not. The firefighters have been doing it for several weeks and talks are now ongoing about how to open it up to the public more broadly.
Feng Zhang has used the CRISPR Cas-13 protein’s unique properties to develop a diagnostic method called SHERLOCK. “We started with RPA as a different way of amplifying RNA and then combining that with the CAS-13 protein to be able to carry out detection.” Dr Zhang is a co-founder of Sherlock Biosciences. In April they received FDA emergency use approval for a SHERLOCK test that uses LAMP amplification coupled with Cas-13 detection for use in a clinical lab setting.
In his academic lab, Dr Zhang has been developing another easy-to-use diagnostic methodology by combining the amplification and the CRISPR detection into a single reaction to avoid contamination. This new method – called STOP, which stands for SHERLOCK Testing in One Pot – gives a paper strip readout in minutes. He and Dr Mason are now collaborating to test this technology on patients. “One of our collaborators in Thailand, who used our original protocol of RPA followed by Cas-13, was able to get approval from his hospital to begin using it to triage patients who are coming in for surgery.”
“Here in the US,” Dr Zhang continued, “we are now trying to also build a very low cost, simple device so that people can run these tests in a more turnkey fashion without having to do very much. They just take a swab and then put it into the reaction.”
In order for these tests to become available to the general public, however, Mason and Zhang both agree that two parameters have to be met. “Number one is scale,” said Dr Zhang. “The tests and devices have to be able to be manufactured at an extremely high scale. The FDA says that they want to achieve one million tests per day by the late fall or winter this year. To get to that kind of volume it really is not going to be just one manufacturer. It's going to be many, many different manufacturers working together to be able to meet that volume. And the second parameter is that it has to be super easy to run - and quick. And I think these LAMP-based methodologies, or STOP with a device, will get us close to that.”
Dr Mason agreed, “I feel like three tiers of testing are probably needed. Centralized labs run on really big machines which already exist for thousands of samples is the high-level tier. The medium tier is where you have a small device like this at pop up labs or drive-through testing at pharmacies or places like that. We’ve been focusing on this medium tier where the LAMP technology is already FDA approved for use. But eventually the third tier will be home testing, like a pregnancy test.”