4basebio
Manufacturing high-quality synthetic DNA for the genetic medicine revolution
The challenge
High-quality DNA is in demand for gene therapies and vaccines to treat cancer and many other rare and devastating diseases. It’s also the starting point for mRNA vaccines, such as those used to protect people against COVID-19.
Conventional DNA manufacture involves inserting the required gene into a bacterial plasmid. But this introduces safety issues, such as the risk of integrating antibiotic-resistant genes, bacterial contaminants, and endotoxins within the final product. Novel, synthetic DNA production methods could help get genetic medicines to people faster, with an enhanced safety profile compared with plasmid DNA.
Cambridge-based SME 4basebio has developed an enzyme-led manufacturing process that avoids using plasmids. This approach is safer and faster because it avoids the cumbersome fermentation processes required for plasmid DNA and eliminates bacterial contaminants.
As a start-up with limited bandwidth, 4basebio accessed CPI’s specialist expertise and state-of-the-art biologics facilities to scale-up and improve a central step in their purification process. We introduced a DNA polishing tool to remove impurities, developed analytical methods for checking product quality, and reviewed the regulatory landscape to ease their path to market.
![](https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=1920&h=1080&q=60&fm=jpg&fit=crop&dm=1685108624&s=e0f79a810dce46d78a7f7faad7666a51 1920w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=1120&h=630&q=60&fm=jpg&fit=crop&dm=1685108624&s=f08269510de64969ab25f6a6738b01ec 1120w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=2240&h=1260&q=45&fm=jpg&fit=crop&dm=1685108624&s=e42a6d8b0eafb41a8de1838a1ba16a71 2240w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=800&h=450&q=60&fm=jpg&fit=crop&dm=1685108624&s=069dc8bc1f6548c510899ab180ee986d 800w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=1600&h=900&q=45&fm=jpg&fit=crop&dm=1685108624&s=7f0676839b16cb79b5b30836e0b46547 1600w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=480&h=270&q=60&fm=jpg&fit=crop&dm=1685108624&s=af62cb21d82de478007759fd145ffd2f 480w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-purification-2-4basebio.jpeg?w=960&h=540&q=45&fm=jpg&fit=crop&dm=1685108624&s=08ff975e2c3c34a0d0fe39d054a9bbd7 960w)
“CPI helped us accelerate a vital aspect of our manufacturing process to expedite our journey towards a clinical product. We’ve made significant progress in our GMP manufacturing capabilities, leading to our first DNA sales and increased interest in our products from partners and client base.”
![Carmen Mañas Torres Carmen Mañas Torres](https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/Carmen-4basebio.jpg?w=100&h=100&q=60&fm=jpg&fit=crop&dm=1685629150&s=1f90347affd4c74455310ff48dbf2a24)
How CPI helped
- Developed analytical approaches for assessing the quality of the DNA product using high-performance liquid chromatography (HPLC).
- Provided support with scaling up and improving the downstream processing of DNA using tangential flow filtration (TFF).
- Screened different materials and protocols for the final polishing step after DNA purification.
- Consultancy around the regulatory landscape for DNA as a therapeutic starting material – such as in the manufacturing of RNA and adeno-associated virus (AAV) – or as a therapeutic itself.
- Ran a comparison between the client’s DNA and existing products on the market.
![](https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=1920&h=1080&q=60&fm=jpg&fit=crop&dm=1685109178&s=5a037c4caa8c78202e2f436524f8a7f9 1920w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=1120&h=630&q=60&fm=jpg&fit=crop&dm=1685109178&s=38b0eeb3898da01bc2680c46dba8e765 1120w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=800&h=450&q=60&fm=jpg&fit=crop&dm=1685109178&s=510bc8319a5143fb04b8dfe558bc3c40 800w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=1600&h=900&q=45&fm=jpg&fit=crop&dm=1685109178&s=391ceddca9f36d9a8936c49eebcced95 1600w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=480&h=270&q=60&fm=jpg&fit=crop&dm=1685109178&s=eca6cb23dc04ba2149499a42b266b83b 480w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/CPI-4basebio-edited.png?w=960&h=540&q=45&fm=jpg&fit=crop&dm=1685109178&s=6af4f83a82b88b65aeaf2af5e5a9c0d9 960w)
Achievements
- Developed a method for downstream purification of synthetic DNA using TFF to create a higher-quality product.
- Developed HPLC approaches to analyse impurities in the product twice as quickly and more effectively than with standard chromatography.
Impact
Our consultancy enabled 4basebio to improve the speed of their production process and the quality of their DNA products. With the support of our biologics expertise and equipment, they have progressed more quickly towards clinical application.
Ultimately, 4basebio’s DNA could be used to create powerful new genetic medicines able to transform lives and respond rapidly to unmet clinical needs, with improved safety, turnaround time, and cost benefits compared with conventional plasmid-derived products.
Producing synthetic DNA is also a more sustainable approach, requiring fewer resources than traditional techniques that use bacterial plasmids. This significantly smaller manufacturing footprint contributes towards the future of genetic medicines while having less impact on our planet.
This collaboration was part of our SPRINT (Supporting Process Innovation for Novel Therapies) project, funded by the European Regional Development Fund (ERDF). Over the last 2 years, SPRINT has helped over 40 companies across the Cambridge and Peterborough Combined Authority LEP Region develop their innovations and accelerate their routes to market.
Partners
![HM Government](https://optimise2.assets-servd.host/smart-hoopoe/production/content/logos/HR-Gov.png?w=400&h=222&q=100&fm=png&fit=crop&dm=1686661222&s=3daf17d99851df527b373c791d3044f1)
![European Regional Development Fund](https://optimise2.assets-servd.host/smart-hoopoe/production/content/logos/ERDF.png?w=400&h=89&q=100&fm=png&fit=crop&dm=1686661419&s=d7c52c1afed369d71818af9a42d17e77)
![](https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=1920&h=1080&q=60&fm=jpg&fit=crop&dm=1685108542&s=402e890b027f60002add25472c331a77 1920w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=1120&h=630&q=60&fm=jpg&fit=crop&dm=1685108542&s=76a376bdf8c1d3cea0340b3cd92db623 1120w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=2240&h=1260&q=45&fm=jpg&fit=crop&dm=1685108542&s=3427318c28fa27032a7c5ffaa35ae24d 2240w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=800&h=450&q=60&fm=jpg&fit=crop&dm=1685108542&s=7c50c54bebcab90397bd78c2f9c76250 800w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=1600&h=900&q=45&fm=jpg&fit=crop&dm=1685108542&s=74985b9dca42010677a7e492be38d114 1600w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=480&h=270&q=60&fm=jpg&fit=crop&dm=1685108542&s=b57d5602a21fc6a5d0086b8619dcefdd 480w, https://optimise2.assets-servd.host/smart-hoopoe/production/content/images/DNA-Purification-4basebio.jpeg?w=960&h=540&q=45&fm=jpg&fit=crop&dm=1685108542&s=51ae19d3fb25506c59dd2bd42fb784f0 960w)