Methods for producing nucleic acid hybridization probes that amplify hybridization signal by promoting network formation

Abstract

This invention describes methods for the generation of nucleic acid probes that improve the sensitivity of hybridization assays. The sensitivity increase results from structural modifications of nucleic acids that promote network formation during hybridization with the result that a single target molecule becomes attached to a complex of many probe molecules. The structural modification involves fragmentation of the probe nucleic acid followed by joining the fragments together such that their order and orientation and number is altered from the original probe molecule. The result is the generation of permuted probe libraries. Probes made according to this invention can be used in many kinds of hybridization assays including Southern blots. Northern blots. Dot blots. Nucleic acid Array hybridization, ‘in situ’ hybridization with fluorescent or other labels (FISH) and various kinds of sandwich hybridization assays.

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