Smithkline Beecham Corporation

Ribotargets Limited

Catherine Denise Prescott

Jonathan Karn

The invention relates to a solution-based assay for identifying RNA binding compounds, based on competition. The assay comprises a reporter molecule carrying a fluorescent or chromogenic group that can form a one-to-one complex with an RNA target molecule carrying a second fluorescent or chromogenic group in such a way that the two groups are in sufficient proximity for fluorescence resonance energy transfer and/or quenching to take place. Addition of a compound-to-be-tested prevents formation of the complex and thereby increases the fluorescence of the RNA target and/or reporter molecules relative to the signal obtained in the absence of the test compound. The invention also provides for quantitative screening methods and kits are also included.

Methods and kits for discovery of RNA-binding compounds

This invention relates to a method of screening for compounds that modulate gene expression, particularly those which lower gene expression.

Method for modulating gene expression

Methods are disclosed for identifying an RNA fragment that mimics the structure of a defined or undefined target RNA molecule to which a compound binds inside of a cell resulting in retardation of cell growth or cell death. Methods using these RNA fragments for identifying unknown compounds of pharmaceutical interest, and for identifying unknown RNA targets for use in treating disease are disclosed. These methods and compositions are used in screening for novel antibiotics, bacteriostatics, or modifications thereof or for identifying compounds useful to alter expression levels of proteins encoded by mRNA. The methods involve providing random DNA fragments from DNA which encodes RNA target molecules, cloning such fragments to create a plasmid library of same; transfecting cells which contain the native RNA target molecule with the plasmid library and exposing the cells to one or more of test compounds. Cells transfected with an RNA fragment that mimics the target molecule will survive in culture, and cells transfected with fragments which do not mimic the molecule will suffer defects in growth. The mimicking RNA fragment is isolated and provides structural information about the target. The fragment and the information derived from it are then used to screen or design binding compounds.

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Cambridge, United Kingdom

Catherine Denise Prescott