September 18, 2012
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Despite recent leaps in artificial synthesis of long custom DNA sequences and the hype surrounding similar large-scale projects (e.g. the first synthetic genome), the process is far from mainstream. Synthesis of genes or even minigenes is still expensive, slow and tedious. As a lazy scientists who despises cloning and prefers to synthesize the whole construct at the touch of a button (or a click of a mouse), I am all for methods that advance this area of biotech. So, I am very excited about this paper that recently showed up in Nature methods (and I think it’s pretty smart).
The rationale here is based on the fact that short-DNA (i.e. oligonucleotide) synthesis, which forms the basis for longer molecules, is still very error prone and finding a molecule without mutations requires the direct sequencing of many instances from the final product (only a small fraction of the final products are mutation-free). Now, here, what they have accomplished is that they have successfully shifted the sequencing step to the oligo level. Basically, they tag all the oligos to be synthesized with random barcodes. They sequence the whole population using high-throughput sequencing, identify the correct oligos and use their barcodes to enrich them from the initial population using specific primers and PCR.
I assume companies that synthesize custom DNA can take advantage of a sequencing run to find the correct oligos for multiple independent orders, thus significantly reducing the cost of sequencing. However, high-throughput sequencing is still slow. So, I assume this method doesn’t significantly cut the time requirement of the production phase… but I’m not too familiar with the industrial pipeline, and maybe it does help. I think we’ll know soon enough.