The COVID-19 pandemic demands action on many fronts, from prevention to testing to treatment.
Not content to focus its research efforts on just one, the laboratory of George Church, Ph.D., in the Blavatnik Institute at Harvard Medical School (HMS), and the Wyss Institute for Biologically Inspired Engineering at Harvard University is tackling the problem from seven different angles.
Partnering with various colleagues, the team’s goals are to:
- Create simple, cheap, more accessible testing for SARS-CoV-2, the virus that causes COVID-19, both in humans and on various surfaces.
- Develop a faster way to identify antibodies that neutralize the virus.
- Generate lung tissue models called organoids to test candidate drugs for COVID-19.
- Harness the power of individual genomes to identify variants that raise or lower people’s risk of serious illness when infected by SARS-CoV-2.
- Increase mask use in public.
- Develop public health strategies.
- Identify antibodies that inadvertently help the virus enter cells so researchers who are developing vaccines can avoid including those antibodies.
The projects “get at different parts of the elephant,” said Church, the Robert Winthrop Professor of Genetics at HMS, comparing the many facets of the pandemic to the parable about several blind men who are each touching different parts of the animal and unable to characterize it as a whole.
“It’s too late for certain types of prevention” to contain the spread of the new coronavirus, he said, but there are opportunities to pursue other interventions in the short- and long-term that could save lives.
Most HMS labs have transitioned to remote work following institutional guidance intended to contain the spread of the virus, but some have been granted permission to continue on-site work for COVID-19-related projects. A small fraction of the Church lab is among them.
“We, like some other research labs, already had projects that were adjacent to COVID-19, so it was not hard for us to pivot a little bit,” said Church, who is a Founding Core Faculty member of the Wyss Institute, and leader of the Institute’s Synthetic Biology platform.
Church and Ting Wu, Ph.D., HMS professor of genetics and principal investigator of the genomics-focused project, have applied for funding through the HMS-led Massachusetts Consortium on Pathogen Readiness, or MassCPR. Although the winning applications have not yet been announced, Church said he will find a way to pursue the work regardless. Wu is also an Associate Faculty member of the Wyss Institute.
The first three projects are described below.
Building better tests
It’s become clear that there aren’t enough tests in the U.S. to identify everyone who is sick with COVID-19, let alone to detect people who are infected with the new coronavirus but experiencing mild or no symptoms.
The lack of population-wide testing hampers efforts to accurately assess—and stop—the spread of SARS-CoV-2.
“A number of us are convinced that the big difference between the places that are doing well and the ones that aren’t are high levels of testing,” said Church.
Many groups are striving to overcome testing bottlenecks by ramping up test production and processing and by investigating ways to improve the efficiency and accuracy of the tests themselves. The Church lab has joined their efforts.
The lab is exploring two paths. First, the researchers are trying to develop a tool that can process up to 1 million samples per day. That would be a vast improvement over current testing capacity, estimated to be 160,000 samples per day in the entire U.S. as of April 15, according to The COVID Tracking Project—not enough to cover even those who are symptomatic.
Right now, nasal and throat swabs are sent to labs, where technicians determine whether a given sample contains the new coronavirus by isolating any viral RNA, turning it into DNA and then using a test known as PCR (polymerase chain reaction) to amplify the DNA to detectable levels. The method has several drawbacks, including the limited number of testing slots, or wells, on a PCR plate—typically 96 or 384—and the time and money it takes to synthesize the millions of unique DNA snippets called primers needed to amplify the virus’ genetic material.
Church and colleagues intend to bypass these hurdles by giving each anonymized patient sample a unique genetic bar code; mixing hundreds of thousands of samples together; and amplifying the viral RNA in them all at once using a simpler alternative to PCR known as isothermal amplification, which isn’t limited by number of wells. When the results are spit out in bulk at the end, the bar codes make it clear who is positive or negative for the virus. The method requires only 72 primers, saving additional time and money.
The team would then partner with clinicians and diagnostic laboratories to make sure people can operate the tests in real-world settings and that the devices meet FDA requirements.
It’s not yet clear whether samples would be collected only in health care settings or whether people could receive collection kits at home and mail them to central testing facilities.
