Genscript’s Five-Step Mission To Neutralize COVID-19

Of the 4.2 million COVID-19 case in the world, 1.3 million are in the US, the highest of any country. And the US death toll just passed 83,000, about one-third of the world’s fatalities from the virus.

In China, where the outbreak began, the amount of new cases has fallen tremendously since peaking in February. That country seems to have the worst behind it. With the various strategies different countries are implementing, not to mention uncontrolled variables, it can be difficult to assess whether these strategies are actually working. But one thing is true: countries’ strategies vary greatly. 

In early April, 42 states in the US issued shelter-at-home orders. Today, only 11 states are shut down or restricted, with the rest having partially reopened or planning to reopen soon. The shutdowns and restrictions were put in place to prevent the spread of COVID-19, but they also came at a cost. A record 20 million American jobs were lost in April, with unemployment rates rising to 14.7%. 

Sweden took a completely different approach and did not issue any strict shutdowns. Instead, it encouraged citizens to practice voluntary social distancing. Sweden’s businesses and economy have not been hit as hard as the US, but Sweden has a significantly higher death rate per capita (about 360 per million Swedes versus about 270 per million Americans). 

It will be difficult to assess which governments adopted the best strategies until the COVID-19 crisis is over. But how does the situation look from a scientist’s perspective? What would their game plan be? I asked Liusong Yin, one of the scientists on the front lines in the battle against coronavirus, for his thoughts.

Liusong is the Executive Director and Head of Biologics Discovery at Genscript, a biotechnology company specializing in life sciences research and early-phase drug discovery. Liusong is based in China, where the shelter-in place orders have made the streets unusually empty. But on February 4, 8 mice immunized against COVID-19 were police-escorted 1,200 miles across China. Why? To get to Genscript’s state-of-the-art labs.

In 12 hours, Liusong’s team had successfully screened specific antibodies that recognize viral proteins and potentially block binding of virus to cellular receptors. In less than 24 hours, using the Beacon single-cell platform designed by Berkeley Lights, GenScript had isolated and amplified immune cells from the mice. That process normally takes three months.

Liusong was looking for antibodies that the mice had produced against the coronavirus. The hope was that some of these antibodies could help develop a coronavirus vaccine for humans. Antibodies are proteins found in blood that specifically bind to antigens (a foregin molecule or structure, such as a virus or a pathogen). 

Within 24 hours, Liusong had initiated his five-step plan to find and isolate the specific antibodies responsible for coronavirus immunization:

Binding

The first step is to screen for antibodies that are able to bind to the receptor-binding domain (RBD) of the coronavirus protein. Like two puzzle pieces fitting together, the antibody and the RBD of the virus must “fit together” and bind.

Blocking

The second step is blocking. Once you have found antibodies that are able to bind to  the RBD of the viral protein, you must check that they also inhibit the virus from binding to receptors in the host’s own cells, and thereby prevent it from infecting the host (which in the case of COVID-19 is the ACE2 protein). So blocking is really stopping the virus from binding to the host’s receptors.

Neutralization Test In “Dead Virus”

The third step is to check whether the antibodies that both bind and block the virus can also neutralize the virus. To do this you first use a pseudo-virus, or a “dead” virus. It is like the actual virus but lacks the ability to replicate itself. This is a safety measure, as the real, live virus is quite dangerous (and you need certain laboratories and safety levels to work with it). You then start with testing your antibodies against the pseudovirus to see if they can neutralize the virus.

Neutralization Test In Live Virus

Once you have proven that your antibodies are able to bind, block, and neutralize the pseudovirus, it is time for the live virus. The fourth step is to check whether your antibodies are able to neutralize the real, live virus.

Protection Model In Animal Screening

So far, all steps have taken place “in vitro” in test tubes. But often in science what you see in a test tube may not be true in the real environment. The final step is to test the antibodies in live animals, to see if they provide protection against the live virus. Now  that you have proven your antibodies provide effective protection, you can sequence the genetic sequence of them (their “blueprint” if you will) to produce them at a higher scale. Then you can slowly begin to make your way towards human trials, and hopefully end up with a successful vaccine against the coronavirus.

These five steps seem straightforward, so why does a coronavirus vaccine take so long? When will one be ready? 

The process takes a lot of time and it is a challenging task. Genscript is working hard and has been operating at full capacity to accelerate this coronavirus research. Luckily, they are not alone in this fight, as they provide various services to other companies who are also in this battle. In addition, Genscript collaborates and partners with companies and institutions on the mission to neutralize COVID-19. 

Among Genscript’s allies is Mount Sinai Health System, with whom Genscript is developing antibodies to block the coronavirus from entering human lung cells. Another collaborator is the Chongqing Academy of Animal Sciences and Chongqing CAMAB Biotech Ltd. that Genscript began a collaboration with back in January to initiate an emergency screening project using the Berkeley Lights Beacon single-cell platform screening technology. 

With many initiatives to fight COVID-19, Genscript has also been cited and acknowledged for their coronavirus research-accelerating products and services in more than 42 publications. In addition, Genscript is also sharing knowledge and advice about peptides, proteins and plasmids for COVID-19 detection and research through MolecularCloud. 

And just last week, Genscript announced cPass, the world’s first test that allows rapid detection of neutralising antibodies, without the need of live biological materials and biocontainment facility, along with Duke-NUS (Duke-NUS Medical School) and A*STAR (Singapore’s Agency for Science, Technology and Research).

Although these are uncertain times, one thing I am certain of is that with synthetic biology and life sciences companies stepping in to help from all around the world, scientists like Liusong Yin may soon defeat COVID-19. 

Follow me on twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters in synthetic biology Thank you to Stephanie Michelsen for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about—including Genscript—are sponsors of the SynBioBeta conference and weekly digest — here’s the full list of SynBioBeta sponsors.