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Hybridization prediction gets to first base

Nature Biotechnology volume 17, pages 751–752 (1999)Cite this article

All oligonucleotide-based technologies that target mRNAs, from microarray analysis to antisense- or ribozyme-based strategies for gene therapy, require Watson-Crick base pair binding of the effector molecules to their target sequence. However, there are virtually an infinite number of potential target sequences contained within any given mRNA. Unfortunately, despite some elegant computational attempts1, there currently is no way of readily identifying optimum target sites, or even those that are simply active. If antisense technologies are ever to make the big leagues, the factors that determine the characteristics of heteroduplex formation must be established. In this issue, Mir and Southern2 have successfully used a rationally designed oligonucleotide array to identify oligodeoxynucleotides than optimally hybridize to a target tRNA. While not a home run, their approach is a good solid single and perhaps the start of a rally.

The crux of the problem facing the genomics community is that with the anticipated completion of the Human Genome Project, tens of thousands of gene sequences will be available, and RNA-directed oligonucleotide technologies, at least in theory, offer some of the best methods for the determination of gene function. But the frustrating bottleneck of determining an optimal targeting region on the mRNA has severely limited these kinds of exciting applications, and will continue to do so unless wasteful empiric targeting strategies can be eliminated.

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Figure 1: Schematic representation of the binding of tRNAphe to an array of complimentary oligonucleotides immobilized on a glass plate.

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  1. associate professor in the Departments of Medicine and Pharmacology at Columbia University, New York , 10032, NY

    C.A. Stein

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  1. C.A. Stein
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Stein, C. Hybridization prediction gets to first base. Nat Biotechnol 17, 751–752 (1999). https://doi.org/10.1038/11680

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