Gene Synthesis Gets Cheaper

A new method for synthesizing specific DNA sequences could revolutionize the production of genes in the laboratory (Nature, 23 Dec 04, Vol. 432, No. 7020, pp. 1050-1054). The technique, which uses programmable 'DNA microchips', looks set to slash the current cost of gene synthesis.

The DNA microchips are tagged with thousands of different short DNA sequences called oligonucleotides. These form two groups: 'construction' oligonucleotides, which act as templates for the replication of corresponding genetic sequences, and 'selection' oligonucleotides, which reinforce production of the correct sequences to minimize errors. A single-step reaction then assembles these short DNAs into much longer stretches of sequence.

To test their method, George Church and his colleagues assembled all 21 genes used by the bacterium Escherichia coli to create one part of its protein-assembly apparatus, called the ribosome. By tweaking the sequences of the construction oligonucleotides, they were able to increase the efficiency with which these genes were translated into protein, bringing closer the goal of creating a complete artificial ribosome in the lab. If successful, the technique could radically cut the cost of assembling gene sequences, which currently yields about nine DNA 'letters' for every dollar spent. The researchers hope that with this new method, a dollar could potentially buy 20,000 letters of highly accurate code.

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