What Does It Take to Build a Biofoundry for Therapeutic DNA Manufacturing?

Biomanufacturing expert Nicolas Moniotte breaks down seven practical questions to consider before getting started.

Biology is becoming increasingly programmable. For mRNA vaccines and personalized therapies, the required sequence may change from one program, or even one patient, to the next. Manufacturing must be able to respond with greater speed, flexibility and control. Bringing DNA manufacturing in-house through a biofoundry offers a practical route to achieving this. It can give organizations greater control over quality, timelines and supply while creating a consistent manufacturing pathway from preclinical development towards GMP production. In my experience across R&D, CMC and manufacturing, these projects are most successful when a biofoundry is treated not simply as an equipment purchase, but as a broader manufacturing strategy. A biofoundry brings together DNA synthesis, assembly, correction and amplification within an integrated workflow capable of producing consistent, scalable DNA for therapeutic applications. Although establishing this capability requires careful planning, many of the underlying facility, quality and operational requirements will already be familiar to experienced biomanufacturing teams. The following seven questions provide a practical starting point.

1. Will GMP fit into your plans?

A biofoundry can have broad applicability, from academic and translational research institutions to clinical-stage developers, CDMOs and academic medical centers. It can support research and preclinical development as well as the production of DNA for therapeutic manufacturing. Organizations with established GMP experience will generally have the most straightforward route to implementation. They are likely to have many of the necessary facilities, quality systems and experienced personnel already in place. However, the absence of current GMP capability does not preclude an organization from establishing a biofoundry. The important first step is to define how the facility will be used today and how its role may evolve as programs advance. In the workflow proposed by DNA Script, oligonucleotide synthesis, assembly and correction can take place outside a full GMP environment. When DNA is intended for clinical manufacturing, these operations must be appropriately separated from the final in vitro amplification step, which is performed within a GMP suite. Planning this boundary early allows research institutions to establish valuable DNA manufacturing capabilities now while retaining a clear path towards future GMP production.

2. Have you planned the complete workflow?

When people first hear the term “biofoundry,” they may picture a single automated instrument. In practice, it is more useful to think of it as a complete manufacturing workflow, and that is where much of its value lies. The process begins with a digital DNA sequence and progresses through oligonucleotide synthesis, assembly and correction, and amplification. Each stage has its own equipment, space and operating requirements, but the objective is to bring them together as one controlled and repeatable process. Organizations should map the complete workflow before defining the facility footprint. This includes the separation of GMP and non-GMP activities, the movement of materials and operators, water requirements, cleaning procedures and the use of single-use consumables. The utilities themselves are not necessarily unusual for a biomanufacturing facility. The opportunity lies in integrating the individual stages into a streamlined system that can consistently move from a digital sequence to scalable DNA for in vitro transcription.

3. Do you have the right team and quality systems?

The encouraging point is that organizations already manufacturing under GMP will generally have much of the required capability in place. This includes quality assurance, quality control, established quality systems and operators familiar with GMP procedures. Even for organizations building these capabilities, a biofoundry can be treated as one workstream within a broader GMP manufacturing program. Establishing the workflow should not require the recruitment of an entirely new team of DNA synthesis specialists. With suitable training and support, existing technical and quality teams can form the foundation of the operation. One capability that should not be overlooked is sequence design. A manufacturing platform can translate a defined RNA sequence into the corresponding DNA template, but designing the RNA itself, including the sequence encoding a selected antigen, is a separate area of expertise that must be available internally or through a partner.

4. Where does automation add the most value?

Automation can improve reproducibility, reduce hands-on time and make sophisticated manufacturing workflows easier for operators to adopt. Upstream activities such as oligonucleotide synthesis and assembly can be highly automated. Other operations, including certain in vitro amplification steps, may continue to use established manual GMP procedures. This does not need to be seen as a limitation. The objective is not automation for its own sake, but a controlled and repeatable process. Automated and manual steps can work effectively together when each has a clearly defined role, supported by appropriate procedures and training. Automation can also reduce the amount of specialist training required. For the manual elements, operators can be guided through the workflow step by step, initially working alongside an experienced scientific support team before completing subsequent runs independently.

5. What are some of the biggest advantages of establishing a biofoundry?

One of the biggest advantages is greater control over DNA quality. Outsourced production provides convenience, but the customer may have limited visibility into the manufacturing process itself. With a biofoundry, quality becomes a visible and controllable part of the workflow, from the fidelity of the oligonucleotide building blocks through assembly, correction, amplification and release testing. This allows quality to be considered throughout production rather than only assessed once the finished DNA is delivered. Teams can monitor individual stages, understand the factors affecting performance and continuously improve the process as their experience grows. A biofoundry also brings these stages together within a streamlined workflow. Building the same capability independently, by sourcing individual technologies, establishing separate processes and then integrating them, could take months or even years. An integrated approach can reduce that burden while making more efficient use of both time and facility space. Analytical methods are an important part of this control. GMP-grade release assays, transferred standard operating procedures and additional characterization methods allow teams to determine whether DNA is suitable for release, monitor overall quality and investigate deviations when they occur.

6. What will it take to become operational?

Becoming operational should be viewed as a guided implementation process, rather than an open-ended effort to develop every element from scratch. Physical installation can potentially move relatively quickly once the equipment has arrived. However, organizations should also plan for shipping and export requirements, installation qualification and operational qualification, operator training, analytical-method transfer and the transfer of any manual amplification procedures. I find it useful to think of a well-supported biofoundry as being closer to a turnkey installation than a collection of components delivered with a set of instructions. Installation, training, method transfer and on-site scientific support should work together to help the organization establish the complete workflow. Support during the first production runs can be particularly valuable. Operators can complete the workflow alongside experienced specialists, repeat it with guidance and gradually build the confidence to run it independently.

7. When does a biofoundry make sense?

A biofoundry will not be the right choice for every organization. Outsourcing may remain more practical for early research, occasional DNA requirements or programs that are unlikely to progress towards GMP production. The case becomes much stronger when GMP manufacturing is a clear part of the development roadmap and there is a recurring need for high-quality DNA. This may include CDMOs supporting several clients, clinical-stage developers with expanding pipelines, or academic medical centers preparing to manufacture personalized vaccines. The decision is not based on production volume alone. Process continuity can be equally important. The same core DNA manufacturing workflow can support late preclinical, toxicology and GMP production, reducing the need to introduce and validate a different process as a therapy advances. Cell-free DNA manufacturing can also avoid some of the time and complexity associated with establishing and validating cell banks or monitoring genetic drift. Instead, organizations can repeat a defined process to produce consistent material across successive stages of development. Together, these advantages can shorten timelines, make more efficient use of facility space and reduce the manufacturing risk involved in moving programs towards the clinic. This can be especially valuable for organizations supporting multiple programs or developing personalized therapies where manufacturing must respond quickly to changing sequences.

Building the foundation for on-demand manufacturing

Establishing a biofoundry is a meaningful manufacturing decision, but it does not mean developing every capability from the ground up. Many of the necessary utilities, quality systems and operational skills will already be familiar to GMP manufacturing teams. An integrated workflow, supported by training, analytical methods and scientific expertise, can make the remaining steps much more manageable. From my perspective, the opportunity is not simply to manufacture DNA on site. It is to bring greater control over quality, timing and process knowledge inside the organization—and to create a manufacturing capability that can be repeated and improved as programs advance. For organizations with a credible path towards GMP and a growing need for therapeutic DNA, a biofoundry can provide a practical foundation for faster, more responsive production of vaccines and other personalized therapies. As these modalities continue to develop, the ability to move efficiently from a digital sequence to controlled DNA production, without rebuilding the manufacturing process for every new program, will become increasingly valuable.

About the Author

Nicolas Moniotte helps biotech organizations translate scientific innovation into scalable manufacturing. With more than 15 years of experience spanning R&D, CMC and manufacturing, he has built and led teams developing robust, compliant processes for RNA, vaccine and other biotechnology platforms. Applying Quality by Design principles, Nicolas helps companies align technical development, operations, quality and regulatory expectations. He currently supports biotech ventures as an interim executive, CMC advisor and cross-functional operations leader.