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December 17, 2007

Synthetic Biology and Gene synthesis

From the synthetic biology FAQ: Current synthesis costs are about $1 per base pair. Current synthesis times for a 1,500 bp gene are of order 4 weeks. We need a ~3-fold reduction in cost ($0.33 for 3 base pairs) and a ~10-fold reduction in turn-around time (3 days), from where we are today for commercial DNA synthesis to be competitive with standard gene cloning. Such a cost reduction could play out within the next two years; however, changes in turn-around time are much harder to predict.

Geneart is a company offering gene synthesis starting at 0.79 dollars per base pair. Some companies are advertising 0.59 dollars per base pair for 1.5 kb or less base pairs

GENEART AG, the world's leading producer of synthetic genes and specialist in the field of synthetic biology. They had 9 million euros in sales in the first 9 months of 2007 Geneart is profitable. The GENEART AG in Regensburg (Germany) and the subsidiary GENEART Inc. in Toronto (Canada) employ more than 180 people.

Cheap and powerful gene synthesis is at the heart of the impending synthetic life revolution. Building custom organisms could revolutionize the cost and productivity of biofuel production

DNA 2.0 is offering gene synthesis with 8-10 day turnaround DNa 2.0 has made synthetic DNA fragments of over 30 kb and routinely make genes in the 5–7 kb range.


Size Average (days) Median (days)
0–500 bp 8.7 8
500 bp–1 kb 9.3 9
1–1.5 kb 11.1 11
1.5–2 kb 14.5 13
2–3 kb 15.8 14
3–10 kb 26.3 23


A paper on using microarrays to greatly reduce the cost of DNA synthesis (Parallel gene synthesis in microfluid arrays) Written by David S. Kong, Peter A. Carr, Lu Chen, Shuguang Zhang, and Joseph M. Jacobson from
Center for Bits and Atoms, Media Laboratory, Department of Chemical Engineering and Center for Biomedical Engineering, Massachusetts Institute of Technology.

The costs of expensive reagents such as polymerase and oligonucleotides can be significantly reduced by utilizing microfluidic technology to minimize reaction volumes to a fraction of a microliter as compared to tens of microliters required in conventional syntheses.

Further reductions in oligonucleotide costs by several orders of magnitude can be achieved by utilizing the oligos synthesized from DNA microarrays. In such arrays, large numbers of distinct oligos are synthesized massively in parallel [104–105 or more for a single high-density array] but in minute quantities (femtomoles or less). Thus, each oligo in a microarray can cost as little as 1 × 10**−5 to 1 × 10**−3 dollars per base, depending on the array, which typically cost between a few hundred to a few thousand dollars (e.g. USD489 for a 244000 spot Agilent microarray). These costs per base are orders of magnitude less than for conventional oligo synthesis. Thus, the current significant contribution of oligo costs to the overall price of gene synthesis could be reduced to an almost trivial amount if the wealth of raw building material provided by microarrays could be successfully utilized. If maximally employed, oligo costs for building a 10**6bp genome could potentially be reduced to tens of dollars. To achieve this goal, two difficulties must be addressed: (1) conducting synthesis from the low yields of each oligo in a microarray; and (2) problems that arise from manipulating highly complex pools of oligonucleotides (>10**4 distinct sequences). In this work, successful gene synthesis from minute oligo quantities (femtomoles) utilizing a microfluidic device architecture has been demonstrated, while such an architecture employed in conjunction with a microarray has the potential to overcome the limitations associated with complex pool manipulation.


Sales of the gene-synthesis industry are estimated at only $50 million a year, but they are growing rapidly. One foundry, GeneArt, in Regensburg, Germany, has gone public. It says it expects sales this year to increase at least 60 percent, to 12.5 million euros, or about $17 million.

Fueling the surge is the productivity of DNA synthesis, which has increased 700-fold in the last decade, according to Bio Economic Research Associates, a consulting firm. The cost per base pair, the basic chemical unit of a DNA molecule, has dropped to less than $1, from about $30.

Sales of DNA oligos are about $700 million a year, according to BioInformatics, a market research firm, though some executives say that figure is too high. Production is automated and competition is cutthroat, with prices of 10 cents to 50 cents a base.


FURTHER READING
George Church's work to lower gene synthesis and raw DNA synthesis costs. Gene synthesis was $1.30 per bp in 2006, so the cost has more than halved to 0.59 dollars per bp now.

A past article on DNA synthesis costs and projections The parallel microchip array method or George Church's methods need to get commercialized for a major 1000 times improvement in DNA synthesis costs.

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