Why relying on plasmids is slowing down your innovation and what to do about it

In the era of genetic medicine, speed, efficiency, and scalability are no longer optional, they’re crucial. From mRNA vaccines to cell and gene therapies, the demand for high-quality starting materials is growing rapidly. Yet, the industry’s continued reliance on plasmid DNA (pDNA) is revealing critical bottlenecks in both manufacturing and supply. As the industry is evolving, so must the tools we use to progress the development of genetic medicines. It's time to consider new alternatives, developed to transform how genetic therapies are made. Synthetic DNA offers a cleaner, faster, and more scalable solution that meets the demands of next-generation therapeutics.

In a recent interview with Innovations in Pharmaceutical Technology, Amy Walker, Chief Operations Officer at 4basebio, outlined the key advantages of switching from plasmid DNA to synthetic DNA. Below, we highlight the main takeaways from that conversation.

Synthetic DNA: A faster, cleaner and safer alternative to plasmid DNA

Synthetic DNA is produced enzymatically in a cell-free manufacturing process, which offers a faster, cleaner, and more scalable alternative. 4basebio has developed 4 innovative synthetic DNA constructs, each of them offering benefits for their respective downstream applications.

Compared to pDNA, synthetic DNA delivers:

• Speed: from sequence to GMP-grade DNA in just 8 weeks

• Purity: no bacterial contaminants, no antibiotic resistant genes

• Sequence flexibility: enhanced polyA tail stability

• Scalability: smaller production footprint with higher yields

How to make the switch to synthetic DNA?

Companies already using pDNA can transition to synthetic templates with minimal disruption. The process begins with an assessment of how to incorporate synthetic DNA formats into existing production workflows. While some adjustments, such as to analytical methods or release testing protocols may be required, most changes are minor.

As experienced partners, 4basebio can support this transition with regulatory guidance and optimised workflows tailored to your existing processes. Our goal is to help you upgrade to synthetic templates efficiently, with minimal risk and maximum impact

Some developers decide to make the switch during ongoing programs, while others prefer to start with a new development phase. Both strategies have been utilized by many organizations, and both offer advantages. With 4basebio, companies can unlock the benefits of synthetic DNA, while accelerating their development program.

Read the HelixNano case study, to find out how they implemented synthetic DNA for their mRNA vaccine program.

Regulatory considerations

As synthetic DNA gains traction in early-stage clinical research, ensuring regulatory compliance is more critical than ever. Like pDNA produced under Good Manufacturing Practice (GMP) standards, synthetic DNA for clinical use must be manufactured under tightly controlled conditions. Having been awarded GMP Certification for our synthetic DNA production, 4BaseBio products for clinical use fits these requirements. This includes rigorous documentation and full traceability of all materials, processes, and equipment used during production.

To navigate the evolving regulatory landscape, early and proactive engagement with regulatory agencies is essential. Collaborating with regulators from the outset helps align on expectations, design effective comparability studies, and establish robust quality control protocols. This level of transparency not only supports a smoother regulatory review but also builds confidence in synthetic DNA as a viable platform for clinical applications.

Future outlook for synthetic DNA

Shifting to synthetic DNA is an important step for the genetic medicine manufacturing landscape. It’s not just a promising new alternative; it may be the future and help address the challenges of plasmid DNA. Faster timelines, improved safety profiles, and greater scalability make it a compelling alternative to traditional pDNA.

Read the full article written by Amy Walker for Innovations in Pharmaceutical Technology.