There’s a substantial need for high-quality synthetic DNA in the gene therapy development process. Whether it’s for constructing transgene payloads or engineering viral vector delivery systems, researchers count on gene synthesis vendors throughout the discovery, development, and manufacturing journey.
In an article published in The Medicine Maker, Ansa founder and Chief Scientific Officer Daniel Lin-Arlow described the importance of synthetic DNA for gene therapy work — and the challenges faced today by scientists who often can’t get the DNA they need to move these projects forward. The full article is well worth a read, but if you’re short on time, here are some highlights.
‘Suboptimal practices’ from traditional vendors
While designing the needed DNA sequences is a relatively simple process, getting them from a traditional vendor is anything but. The ordering process is plagued by “limitations around guanine-cytosine (GC) content, homopolymers, repeats, and many other elements that fall under the broad category of ‘complex DNA,’” Dan writes. “Across the board, synthesis vendors seem to have convinced scientists that they have no choice but to accept suboptimal practices such as redesigning sequences to meet manufacturing constraints.”
Limiting the potential of gene therapies
The restrictions placed on synthetic DNA orders by traditional vendors are hindering scientists’ ability to develop new gene therapies for a variety of clinical needs. “We cannot realize the full potential of cell and gene therapies without being able to explore a broader design space — and reliably get the actual DNA we want to test all of those interesting ideas,” Dan adds.
Evaluating a gene synthesis vendor
In the article, Dan outlines the major factors to consider for gene therapy scientists looking to order synthetic DNA — and they might not be the ones you’d expect. The ability to manufacture complex DNA, for example, is essential because complexity is the most common reason that sequences get rejected by vendors. Enzymatic synthesis can produce much longer oligos, and this length helps to overcome the complexity issue. “If exploring a larger design space would be helpful for your cell and gene therapy work, look for a synthesis vendor that not only claims to build complex DNA, but also backs it up with specific parameters for how they define (and consistently deliver on) complexity,” Dan writes.
Two other key factors are quality control, which should ideally be done with long-read sequencing to cover the complete DNA product, and turnaround time, which should represent the time it takes to get your complete order, not just the first constructs.
Gene therapy scientists “shouldn’t be limited by arbitrary technical constraints in the DNA synthesis process,” Dan concludes. “It’s time for scientists to have the freedom to focus on their research without being limited by their DNA synthesis vendor.”
Check out the full article and learn more about Ansa’s commitment to complete order turnaround times with the Ansa On-Time Guarantee.
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