Long Chain DNA Synthesis: Unveiling the Missing Piece in the Puzzle of Genetic Engineering
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By Suraj Nair, (Deep Science and Technology Investments, Ankur Capital)
Novel enzymatic processes for long chain DNA synthesis.
What is going on?
Several companies have emerged with innovative enzymatic processes and automation for long chain DNA synthesis. These include the likes of Twist Bioscience, DNA Script, Evonetix, Nuclera, Ribbon Biolabs, Camena Bioscience, Molecular Assemblies, Ansa Biotechnologies and GenScript. These companies are leading the charge in making long chain DNA synthesis affordable and accessible at the lab benchtop. They are targeting applications in designing new drugs, textiles, improved crops, DNA data storage and many more. DNA Script launched its desktop DNA printer in 2021 which can do parallel sequencing and has gone on to raise more than $200 million in January 2022. The company is also launching the most advanced fully automated version of its device which can synthesize an oligo up to 120 nucleotides long in under 24 hours. Similarly, Twist Bioscience launched its enzymatic DNA synthesis kit in January 2022.
What does it mean?
Nucleotide synthesis has progressed at a slow pace. Phosphoramidite synthesis, the technology used generally for DNA synthesis was developed in the 1980s. Although it is an efficient technology, it faces two major limitations: first being the use of highly unstable toxic chemicals (stability of one or two weeks) which makes the process costly when the synthesizers are operated for longer time periods. Secondly, the accuracy or the elongation cycle efficiency of the technology becomes questionable for synthesizing longer chain DNA. Despite the fact that the accuracy of adding individual nucleotides to the chain would be more than 99.6%, even minute errors can have a significant impact on the final sequence generated. These two factors put together have limited the maximum length of DNA sequenced to 200-300 base pairs.
Most of the applications of synthetic DNA currently are limited to short chain sequences such as primers for therapeutic and diagnostic purposes, due to limitations in the synthesis of long chain synthetic DNA. Companies are taking two approaches to counter this problem: automation in parallel synthesis of shorter DNA strands (up to 300 bp) and then joining them (DNA Script, Evonetix) or direct long chain enzymatic DNA synthesis which can be done faster and at affordable costs with minimal errors (Molecular Assemblies).
Why does it matter?
💸For markets: Over time, the demand for synthetic DNA has witnessed a substantial surge, accompanied by a remarkable decrease in the cost per base of DNA synthesis.
While the demand for synthetic DNA has increased over the years, the cost of synthesizing per base has fallen equally fast. Overall, the value of the market has not grown much in these years. The main reason behind this is the fact that you only require one copy of the synthetic DNA which can be used to produce millions of copies naturally using microbial systems, thereby limiting the market demand for synthetic DNA. However, synthesis of long chain DNA can open up new opportunities in producing complex proteins as well as DNA vaccines and gene therapy. DNA storage, where the length of the DNA chain required will be dependent on the amount of information to be stored, is another huge market opportunity that beckons as the cost of long chain DNA synthesis goes down.
🧑🏿🤝🧑🏻For society: Gene therapy and DNA vaccines represent the frontier of personalized medicine enhancing healthcare outcomes for a broad range of patients.
Gene therapy and DNA vaccines are the next frontier in personalized medicine which can drastically improve healthcare outcomes for a large patient population. However, these therapies are currently costly and inaccessible, partially because of the cost of DNA synthesis. Storage of data in the digital binary form today is energy intensive, very costly and highly unsustainable, given the rate at which data is being collected. Synthesis of long chain DNA at affordable costs and without errors can go a long way in making DNA data storage a reality.
🔮What’s next?
Innovation in DNA synthesis technologies is expected to be focused on three objectives: automation to reduce errors and make it more accessible, use of greener sustainable chemicals or enzymes and reducing the cost. Since dangers of the misuse of easy accessibility of DNA synthesis technologies exist, most companies who provide synthetic DNA as a service, appreciate the need for regulatory policies to protect their commercial and reputational interests and are expected to contribute to the development of such policies in the near future.
Note: Read more about Ankur Capital and our work in deep science technologies here: https://www.ankurcapital.com/techsprouts
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