Synthetic DNA Arrays.
Genetic Engineering (N Y) 20:111-123 (1998).

(Note: Current Rosetta Inpharmatics employees are shown in boldface type.)

Alan Blanchard, Rosetta Inpharmatics, Kirkland, WA

Abstract

Analytical techniques that exploit the phenomenon of sequence-specific hybridization between nucleic acids have been workhorses of modern molecular biology. With the exponentially increasing rate of genomic sequencing has come a need for hybridization techniques that can keep pace with this vast amount of information. One way is to exploit the parallelism inherent in using arrays of bound DNA as analytical tools. A convenient format for doing this is to array DNA samples, such as cDNAs or PCR products, on a flat substrate, such as nitrocellulose filters or glass plates. Arrays with several thousand samples on an area of a few square centimeters have been made and proven to be extraordinarily useful, especially in gene expression studies (1-3). But their manufacture is tedious and expensive, due mostly to the effort required to synthesize and purify the DNA samples prior to arraying them. Moreover, using naturally-derived DNA samples limits one to probes that are found in nature and presents the usual handling and logistic problems when duplicating experiments in other laboratories. With the enormous amount of sequence information now available it is possible to consider making the probes synthetically. Over the past several years, a new set of technologies has emerged for making arrays of synthetic surface-bound oligonucleotides for doing hybridization experiments. These technologies and some of the applications for synthetic DNA arrays are the subjects of the review.