Who will fill the gap by making nucleic synthesizers now?

Sir

We would like to draw attention to a looming problem for all those of us doing research involving the chemical synthesis of nucleic acids. Because the main manufacturer has stopped making the equipment we need, we believe that by the end of this year there will no longer be a standard-scale synthesizer manufactured that is really suitable to make DNA or RNA oligonucleotides for research.

Significant areas of RNA research, in particular, require the synthesis of RNA modified in specific functional groups or by the attachment of fluorophores or other reporters. Similarly, antisense oligonucleotide research requires increasingly sophisticated combinations of modified nucleotides and conjugates. For these studies, a research-level synthesizer is indispensable. There will probably be hundreds of laboratories directly affected in the long term, to say nothing of the knock-on effects in the development of the science overall. RNA chemical biology is currently immensely exciting, and moving extremely fast. Yet without the ability to synthesize these molecules at will, the whole field will be very much the poorer.

In our opinion the world leader in the manufacture of DNA/RNA synthesizers has been Applied Biosystems Inc. (ABI). This company produced the venerable 380B and then the 394 research synthesizers. Some time ago it stopped making the 394 synthesizer, and just continued supplying the (in our opinion) inferior Expedite machine. However, it intends to discontinue even that at the end of this year. Thus, although high-throughput machines suitable for preparation of sequencing and PCR primers will still be available, it appears there will be no manufacture of a synthesizer suitable for small-scale, versatile synthesis of nucleic-acid analogues.

No doubt many labs will continue to nurse their existing instruments for some time to come, but as wear and tear take their toll and parts eventually fall into short supply we are likely to lose our ability to make the molecules on which so much exciting research depends. Although ABI has an excellent record of maintaining its obsolete synthesizers, it can give no long-term guarantees of this. Further, if no suitable machines are to be manufactured in the future, this prevents imaginative new researchers coming into the field, which will ultimately have a stultifying effect.

We hope this letter will alert everyone interested in the chemical biology of nucleic acids to this very worrying development. We also hope that it might stimulate a manufacturer somewhere to fill this gap. Our hope is that companies that grew big by selling to the research community might remember their origins, and not turn their backs on the people who have come to depend upon them for their research.

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Lilley, D., Gait, M. & Eckstein, F. Who will fill the gap by making nucleic synthesizers now?. Nature 411, 15 (2001) doi:10.1038/35075244

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