Monday, October 12, 2020

DNA Reads are Cheap, What About DNA Writes?



Thanks to large gains in compute power, the costs to read DNA have dropped exponentially (23andme, Ancestry, etc are the result of this), but the costs to write DNA have only dropped linearly. But there is a lot of work going on in DNA write technologies to address this.

Most synthetic DNA has been made the same way since the early 80s using a serial process known as Phosphoramidite Synthesis.  This method requires attaching each base pair to the existing strand one at a time, and it limits synthetic DNA strands to about 100 base pairs in total length before errors, time, and cost challenges set in. However, a series of companies funded over the last couple of years is seeking to change this, and improve the reliability and economics of writing DNA.


Enzymatic DNA is being proposed as a way to overcome the limits of traditional synthetic DNA construction.  By using an enzyme, in this case Terminal deoxynucleotidyl Transferase (TdT), the addition of new nucleotides can be done without engineering each additional attachment to an existing strand.


To date, enzymatic DNA hasn’t gone much further than traditional synthesized DNA, and has been running at a functional limit of 300 base pairs.  But a series of recently funded companies are looking to expand that limit and reduce the cost of synthetic from the 9-15 cent per base pair range it has been in the last few years.


Among these companies, DNA Script and Nuclera are developing Enzymatic DNA Printers that are planned to hit the market in the next 6-18 months.  Both are following the business strategy Illumina has set in DNA sequencing, by selling hardware to companies to labs.  DNA Script, based in France with a US headquarters near San Francisco raised $50 million in July.  

San Diego-based Molecular Assemblies raised a $12 million Series A last year and has partnered with protein engineering firm Codexis to license enzymatic DNA technology to other companies.  In a recent Nature Biotechnology article, the company referred to its strategy of providing the ink, not the printer.


Bay Area-based Ansa Biotech recently raised $8 million to become an enzymatic DNA service provider, similar to what publicly traded Twist Bioscience currently does with traditional synthetic DNA.  Twist itself is also using traditional synthesis to archive digital with DNA, which recently funded Kern Systems is looking to do as well with enzymatic DNA.


Enzymatic DNA will likely need to get to 500-1000 base pair strands to start to push costs down for synthetic DNA.  In turn, lower costs could stimulate demand for new applications, much as lower costs did for DNA reads and sequencing.  The emerging enzymatic DNA industry is structuring itself for that growth, and within a few years we could see strong businesses develop in writing DNA, not just reading it.


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