高度な DNA合成が可能な時代における、バイオセキュリティの向上

Synthetic biology is the practice of redesigning natural biological systems for useful purposes. Through synthetic biology, researchers can engineer microorganisms to consume environmental pollutants or aid in the manufacturing of sustainable fuels. The potential benefits of synthetic biology are many and profound, but in the wrong hands, while very rare, the tools of synthetic biology could be used to cause harm. As such, the scientific community must take special care to develop safeguards that prevent the misuse of these tools without suppressing growth and innovation in this dynamic field. 

At the core of synthetic biology is synthetic DNA, a tool scientists use for applications ranging from therapeutic development to data storage. Importantly, synthetic DNA is becoming ever more accessible, and as a result, synthetic biology is rapidly growing in terms of capabilities and outputs.

As synthetic biology evolves, so too must biosecurity

Twist Bioscience is one of the leading DNA synthesis providers. Here at Twist, we believe that, as a core technology provider, it is our responsibility to advance biosecurity to help ensure that the world remains a safe place in the biotechnology age. Since our founding, we have engaged with and advised governments and have helped build consortia with other DNA synthesis providers to develop and promote a consistent set of biosecurity best practices. We are constantly, and actively helping to write the biosecurity playbook for DNA synthesis providers. As synthetic biology continues to evolve, so too must the biosecurity safeguards we put in place. Here we shine a light on key biosecurity challenges in the synthetic biology landscape today, and their potential solutions.

Modern Challenges in Biosecurity

At present, there are relatively few documents providing concrete biosecurity guidance to synthetic biologists. Biosecurity at Twist Bioscience follows guidance outlined in the 2010 U.S. Department of Health and Human Services’ (HHS) Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA, the regulations and policy guidance in the U.S. Federal Select Agent Program (FSAP), and the International Gene Synthesis Consortium’s Harmonized Screening Protocol. In addition, as Twist Bioscience manufactures DNA in the U.S., the sale of synthetic DNA is subject to compliance with the U.S. Department of Commerce Export Administration Regulations which define biological sequences that require a license prior to export from the U.S.

Twist Biosecurity expert James Diggans recently wrote about the challenges facing these regulatory frameworks in an article published in Chemical Engineering Progress. Here are two highlights. If you are interested in learning more, take a look at James’ article here.

Decentralized synthesis presents significant logistical biosecurity challenges

In 2010 the HHS issued the Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA, which is currently the only U.S. government guidance document recommending security practices in synthetic biology. The document is targeted to a narrow portion of the synthetic biology supply chain, specifically centralized facilities generating synthetic DNA. However, DNA synthesis is no longer confined to large production facilities. The advent and ongoing development of benchtop DNA synthesis machines forecast a very near future where low-scale DNA synthesis can be performed with relative ease in a decentralized manner. 

Deterring potentially dangerous sequence synthesis is complicated by the lack of a comprehensive list of “black listed” sequences. Diggans explains, “Given the lack of a blacklist of controlled sequences, [benchtop] devices are unlikely to be able to carry out screening entirely onboard. A more likely model will require the devices to connect back to the manufacturer over public networks, sending encrypted sequence data for screening and retrieving permission for a given synthesis request to proceed.”

While sequence screening on these devices may be complicated, it is imperative that manufacturers ensure benchtop DNA synthesis devices perform the same rigorous level of sequence screening as centralized synthesis providers.

Our evolving understanding of engineering biology requires evolving regulations

The challenges surrounding benchtop devices are illustrative of larger issues in regulating synthetic DNA production, namely that our understanding of DNA is ever-changing as is our ability to manipulate it. This poses several challenges, such as how to evaluate the potential threat of entirely novel DNA sequences. 

Ideally, updated guidance from regulatory bodies would include a single source of truth detailing sequences subject to regulatory control, along with a list of algorithms and other resources that can be used by laboratories to help with novel sequence risk estimation, screening, aligning, and annotation. The complexity of doing so, however, means that such guidance is unlikely. 

Updated guidance can close these gaps

Small gains can still be made. For instance, the 2010 HHS guidance stipulated that screening measures should apply to double-stranded DNA greater than 200 base pairs in length. At the time, the assembly of genes using smaller fragments was prohibitively difficult and expensive. Contemporary DNA synthesis makes it possible to efficiently generate vast pools of oligonucleotides less than 200 base pairs which can easily be converted into double-stranded DNA and used to create genes through any of several publically available methods. Updating guidance to recommend screening of pools of DNA fragments (regardless of strandedness) could help close these gaps.

The path forward

Early guidance was drafted at a time when synthetic DNA and synthetic biology were on the precipice of change. Predicting how and where the field would go presented several challenges paired with a risk of slowing scientific advancement. Guidance was thus focused on concrete steps that DNA synthesis providers could take to improve biosecurity in the short term. Now, more than a decade later, we have a clearer vision of what steps can be taken to ensure continued growth in this dynamic field while also ensuring a safer, more secure future.

As leaders in the production of synthetic DNA, Twist Bioscience invests considerable resources in a comprehensive biosecurity program and will continue to both facilitate and champion the responsible and innovative use of synthetic biology and its many applications. To read more about the challenges and potential solutions to modern biosecurity issues, read Diggans’ article, Ensuring the Responsible Use of Synthetic DNA.