HelixNano accelerates mRNA vaccine development with synthetic DNA from 4basebio

HelixNano is a biotech company developing next-generation mRNA technologies aimed at expanding the reach of mRNA vaccines and therapies. Their aim is to address challenges faced by patient populations that traditional approaches often overlook, particularly the immunocompromised and immunosuppressed.

From its inception, HelixNano made a strategic choice to use 4basebio’s synthetic DNA instead of plasmid DNA (pDNA) to manufacture its mRNA drug products. As a company without legacy manufacturing processes, HelixNano evaluated its options and prioritized a technology path that would enable speed, quality, and scalability.

Why synthetic DNA?

HelixNano identified two primary challenges with pDNA that synthetic DNA could address more effectively:

1. Need for long, stable polyA tails

HelixNano required polyA tails to be encoded directly in the DNA template, to bypass enzymatic addition after mRNA production. While this is possible with pDNA, doing so requires the development of a stable bacterial strain capable of maintaining a long polyA sequence, which can be time-consuming, costly, and technically challenging. For a fast-moving company like HelixNano, this approach was not viable.

In contrast, synthetic DNA offers a simpler and faster path with reduced development requirements. The ability to encode a stable polyA tail directly into a cell-free DNA construct eliminates the need for bacterial engineering and enables more predictable manufacturing outcomes.

2. Impurity profiles and downstream mRNA quality

Another concern is the impurity profile of pDNA and its downstream impact. Even after linearization, pDNA can retain residual circular DNA, leading to the generation of high molecular weight side products during in vitro transcription (IVT). These impurities add extra downstream processing steps and affect product quality.

A compelling alternative is 4basebio’s synthetic opDNA® construct. Designed to be linear and open at the 3’ end, opDNA® eliminates the risk of circular contaminants and avoids the need for additional enzymatic linearization or de-ending. This reduces both cost and complexity in the IVT workflow, and minimizes or reduces purification steps  

Why 4basebio?

Among other synthetic DNA suppliers, 4basebio stood out for two key reasons:

• Advanced GMP readiness: 4basebio’s manufacturing platform is GMP-ready, enabling faster progression through regulatory pathways and lowering development risk.

• End-processing efficiency: 4basebio’s DNA constructs are engineered to minimize secondary structures and T7 rollback artifacts issues that can negatively impact mRNA quality. This translates to cleaner and more efficient mRNA output.

Clinical application and impact

HelixNano is currently using 4basebio’s synthetic DNA to power a novel mRNA vaccine platform, designed specifically to induce protective responses in immunosuppressed patients. Their initial clinical trial is nearly complete in Australia.

By adopting synthetic DNA early, HelixNano has positioned itself at the forefront of next-generation genetic medicine manufacturing. The company sees synthetic DNA as a foundational technology that will shape the future of mRNA therapeutics and anticipates broader industry adoption following the first BLA (Biologics License Application) approval using synthetic DNA templates.

How can you transition from pDNA to synthetic DNA

While HelixNano adopted synthetic DNA from the start, companies currently using pDNA can still make a smooth transition. The shift typically requires:

• Assessment of existing processes to accommodate synthetic formats.

• Minimal process adjustments, including minor updates to analytical and release testing protocols.

• Very little optimization, you can simply reduce the dose of DNA required whilst following standard operating procedures

• Strategic timing, such as aligning the switch with a new development phase or clinical milestone.

By partnering with 4basebio, you can simplify the transition to synthetic DNA with expert guidance every step of the way.  We’ll help you design efficient comparability studies, adapt your workflows with minimal disruption, and unlock practical benefits, like shorter lead times, smoother manufacturing, and consistently high mRNA quality.

Conclusion

HelixNano’s experience demonstrates how synthetic DNA can transform genetic medicine development, accelerating timelines, reducing complexities, and improving product quality from the outset. By choosing 4basebio as their manufacturing partner, they were able to avoid the typical challenges associated with pDNA, streamline their IVT workflow, and advance their mRNA vaccine program into the clinic with greater speed and confidence.

If you are looking to stay competitive in a fast-moving therapeutic landscape, synthetic DNA offers more than just a technical alternative, it offers a strategic advantage. Whether you're starting a new program or looking to optimize an existing one, implementing synthetic DNA means gaining access to deep expertise, regulatory-ready processes, and purpose-built DNA constructs designed to simplify manufacturing and deliver reliable results.

If you're navigating long lead times, impurity related setbacks, or pressure to accelerate development, 4basebio is here to help. We’ll work closely with your team to assess your current workflows, guide the transition, and ensure your programs benefit from the speed, safety, and scalability of synthetic DNA, so you can focus on what matters most: getting life-changing therapies to patients faster. Reach out if you would like to explore synthetic DNA for your own mRNA IVT manufacturing.