The COVID-19 pandemic has underlined the necessity of scientific research and development more than ever. One such biotechnology that has been recently developed and has become of great importance to us during the pandemic is synthetic DNA. The term “synthetic biology” was originally conceived by geneticist Waclaw Szybalski in 1970 and refers to the design and construction of various biological parts, as well as the redesign of existing natural biological systems . In the early 2000s, the first synthetic biology conference was held at MIT, which seemed to serve as a marking point of when the field was synthetic biology was beginning to be seriously recognized by the scientific community . Since then, the initiative of the Human Genome Project has allowed for large-scale genome synthesis. In 2019, a team of researchers at the Medical Council Laboratory of Molecular Biology in the United Kingdom became the first group to synthesize and redesign the DNA of the bacterium Escherichia coli . They then created cells with a synthetic version of the altered genome. which had four million base pairs and ran to be 970 pages long. This was a significant milestone and set the precedent for future possibilities through the application of synthetic DNA.
Synthetic DNA has been an instrumental tool for genomic investigation of the virus that causes COVID-19. It has been a pillar for all aspects of dealing with COVID-19, including testing, vaccine development and researching the virus and how it operates . Despite DNA synthesis being such a vital part of COVID-19 research, Thomas Ybert, the founder and CEO of DNA Script in Paris, stated that “lockdowns had affected vital parts of the research and development process to create new treatments and diagnostics, one of which being the synthesis of DNA, which is still generally outsourced to third parties and requires on-demand delivery” . He founded DNA Script with the goal of developing equipment that would allow researchers to synthesize their own DNA molecules within hours without having to outsource the task to a third party. This could be very convenient for the average researcher, who would usually wait several days for molecules to be sent from suppliers.
Ybert says that DNA Scripts’ mission has become even more important and relevant during the pandemic. After the pandemic began and infections began to rise, the demand for quick access to DNA spiked. The PCR test became the most widespread method to initially test people for COVID-19. All PCR tests involve synthetic DNA primers in order to detect the DNA that is potentially present in the sample, so having easy access to synthetic DNA becomes crucial in order to speed up the process of designing better PCR tests . In addition to the use of synthetic DNA in designing better tests for the virus, synthetic DNA was also used to carry out genomic studies of SARS-CoV-2. This research helped provide more information to track the virus’s spread and evolution as time progresses.
With such a high demand for synthetic DNA for research and development, it became apparent that the outsourcing of DNA synthesis was inadequate during the pandemic. This underscored the need to improve methods for DNA synthesis in order to speed up the process and make it more accessible to the average researcher. One of the main weaknesses of the centralized system is that delivery companies such as FedEx and UPS experienced delays, which, in turn, slowed down the arrival of DNA to where it was required. In addition, nationwide lockdowns hindered DNA production centers. In order to combat this issue, there is research being done to make DNA synthesis more efficient. For instance, DNA Script develops equipment that allows labs to produce the DNA that they need in the lab itself, without having to outsource this job . The device they have developed utilizes engineered enzymes to synthesize the DNA molecules within a day. The kits required to make the DNA are able to be stored for months, which allows the lab to sufficiently synthesize DNA during a crisis such as the pandemic.
Another example of an initiative being taken to increase the efficiency of DNA synthesis is the phosphoramidite research being done in partnership with Dr. Alexander Sandahl from Professor Kurt Gothelf’s group and researchers from Professor Troels Skrydstrup’s group at Aarhus University. Phosphoramidites are necessary building blocks in the production of DNA sequences, but they are unstable unless they are stored at a temperature of -20 degrees Celsius. If they are stored above or below -20 degrees Celsius, they degrade quickly. The researchers developed a way to rapidly and easily produce these volatile phosphoramidites instantly before they are used in order to make the DNA production more efficient. The DNA sequences that are being produced by these researchers are called oligonucleotides, which are largely used for disease identification and have many other medical applications. Since phosphoramidites are necessary to produce DNA, but are very unstable, the production of synthetic building blocks is necessary for DNA production. Because oligonucleotides are in such high demand, their production requires an automated method such as the one Sandahl and his group have developed. The operative technology these researchers have created allows the manufacturing of phosphoramidites to be mechanized and integrated directly into the DNA synthesis apparatus, which essentially eliminates the need for manual synthesis.
One example of how DNA synthesis was applied during the pandemic was in the reconstruction of SARS-CoV-2 using a synthetic genomic platform. During the early phase of the COVID-19 outbreak, isolates of SARS-CoV-2 were not available to scientific researchers . However, virus isolates were much needed for the scientific community to develop diagnostic techniques and vaccines. Hence, the ability to use DNA synthesis to replicate the virus helped combat the limited availability of virus isolates and in turn allowed us to create testing tools and vaccines in a shorter period of time.
It is likely that DNA synthesis is going to be more widespread and have many more applications than it does today. DNA synthesis has been used in the development of COVID vaccines, testing and disease identification thus far. Hence, it is important that research on improving the process is continued, so that scientists and health care systems are better prepared for future crises in which synthetic DNA will be very necessary.
Edited by: Ryan Chang