Insight

Enzymatic DNA synthesis is coming

This piece was originally published here

Scientists' ability to manipulate the source code of life, DNA, hinges on the reliably access to sequence-specified DNA fragments. Traditionally, these synthetic DNAs are made using organic chemistry-based methods developed over 40 years ago. Only recently, multiple academics labs and startups (including Nuclera) are harvesting the power of enzymes to improve and potentially replace the way we make synthetic DNA.  

There are notable advantages of using enzymes - faster DNA writing speed, reduced cost, the ability to write longer sequences, the potential to miniaturize the writing process into a portable instrument, and the reduced environmental impact compared to the old methods, just to name a few. Over the last two weeks, there has been some exciting news that brought enzymatic DNA synthesis into the spotlight. 

Last week, DNA Script, a Paris-based startup showed their ability to write 50 bases long, followed by a demonstration that enzymatically synthesized short DNA can be used in a molecular biology application

A few days later, George Church's laboratory demonstrated that using the appropriate coding scheme, enzymatic DNA synthesis can be an effective way to generate DNA fragments for digital information storage purposes.

Finally, just yesterday, Jay Keasling's group showcased a novel way to very quickly write DNA by tethering the building blocks (A, T, C, and G) to an enzyme (think Pac-Man holding on a Pac-Dot) for each DNA addition (see news here).

Based on these recent advancements, it's not too hard to imagine that in the near future, scientists will have access to high-quality, enzymatically produced DNA. One can even imagine a DNA writer that works just like a printer, in which one can input the desired DNA sequences remotely and get the product within a day. To take that one step further, such machine may have the ability to write shorter sequences for data storage or DNA library, longer DNA for genes, and even longer sequences for building and rewriting genomes.

However, we still have some way to go to make an enzymatic DNA writer a reality. As mentioned above, although Keasling's method is fast, the group has so far demonstrated the writing of 10 bases (scientists often use sequences over 1000 bases at a time). While DNA Script has shown a writing length of 50 bases, it is unclear whether the sequence contains all four bases. Finally, in order for enzymatic DNA to be practical in a data storage application, a sophisticated automation solution is needed. 

At Nuclera, we believe that enzymatic DNA synthesis is uniquely suited to be a base technology for such a future DNA writer. This is what we are working towards, so keep an eye on us. Also, over the next few weeks, I will provide some historical context on DNA synthesis, and attempt to show you why enzyme will be the next best thing for DNA synthesis. So stay tuned. 

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