Twist Bioscience
August 26, 2020
4 min read

Why Synthetic is a Better Choice for Viral Controls

Synthetic viral controls offer many benefits over live or attenuated viral controls when screening for infection. Here we deep-dive into why
A qPCR result after a covid test

As SARS-CoV-2 has spread around the world, researchers and companies have raced to develop diagnostic tests, therapies and vaccines to meet the crisis. Positive viral controls are essential components in these efforts, but live viruses can be difficult to obtain, challenging to transport, are dangerous to work with, and require special security laboratories for use.


To overcome this barrier, Twist Bioscience is delivering large quantities of synthetic SARS-CoV-2 positive controls worldwide. These synthetic controls are streamlining critical efforts to develop diagnostics and treatments.


“In a health emergency, like COVID-19, it’s critical that labs have all the resources they need to study the virus and develop countermeasures,” said Twist CEO, Emily Leproust, PhD. “Twist synthetic controls are safer and easier to use than live viruses and give labs access to the viral genomic material they need to innovate.”


Positive controls are especially important when developing NGS and qPCR diagnostic assays, helping researchers pinpoint the reasons behind a negative result. Controls help them differentiate between results that came back negative because there was no coronavirus in the patient sample and those that came back negative because of a flawed test.


Early in the COVID-19 outbreak, live virus was often the primary source for these controls. However, transporting and handling live viral particles poses tremendous challenges: scientists must adhere to a wide array of regulations to ensure worker and community safety, and many labs have little or no experience working with live viruses.


Labs that rely on live viruses for assay research and development may also face viral shortages. These factors combine to slow down essential research, limiting our ability to detect the virus, track community spread and ultimately treat it.


That’s why synthetic controls are so important. Twist’s synthetic controls can be readily shipped and studied in the lab. Because these consist of only synthetic RNA, and not live virus, pathogen containment is no longer an issue, greatly simplifying research workflows.


Equally important, Twist’s high throughput DNA synthesis platform allows controls to be generated in large quantities, alleviating potential shortages. “We are working around the clock to provide critical tools for researchers and test developers worldwide to fight this global pandemic,” said Leproust.


An image of Twist's synthesis chip showing spots where millions of oligos are synthesized
An artist’s rendition showing Twist Bioscience’s high throughput DNA synthesis platform. Millions of DNA oligos are synthesized in a single run.


Also, to abate potential biosecurity concerns, while the synthetic controls encode the entire viral genome, it is fragmented across many smaller molecules, making it very difficult to reconstruct.  Customers purchasing synthetic controls are subject to Twist’s leading biosecurity screening protocols and applicable laws and regulations.


Having a powerful synthetic DNA platform also helps the research community keep pace with this evolving virus. A paper published in early July showed that a variation in a SARS-CoV-2 spike protein made the pathogen more virulent and has been outcompeting the previous version in the United States and Europe. This meant diagnostic labs needed to quickly update their assays in response to the emerging data. Twist launched a new control reflecting this variant within weeks of publication to continue supporting the research community tackling the pandemic.


As bad as COVID-19 has been, the medical and research community are gearing up to face an added challenge – the cold and flu season. COVID-19 shares many symptoms with these less severe cousins. It will be important to quickly triage patients based on their actual underlying virus.


To help address this issue, Twist recently launched controls against several other respiratory viruses, including flu, SARS, MERS and more. These synthetic controls can help clinicians rule out influenza, or a different coronavirus, as well as providing a negative control for SARS-CoV-2.


“The coronavirus has generated the most profound clinical and research challenge in anyone’s lifetime. Fortunately, Twist’s synthetic genetic material, and many other resources, can help us respond. The COVID-19 pandemic is far from over, and we will continue to evaluate market needs where our DNA synthesis platform could provide critical tools to fight disease,” Leproust concludes.

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