Message Pharmaceuticals, Inc.

Alnylam Pharmaceuticals, Inc.

Bearsden Bio, Inc.

Tony Giordano

Deborah L Beach

Gordon Powers

Michael Alan Sturgess

Paul S Eder

Gretchen L Temeles

Catherine Julia Pachuk

Chandrasekhar Satishchandran

Samala J Rao

Venkat Gopalan

Bonnie-Ann Burnett

Milan Jovanovic

David Jacobs

K Asish Xavier

Described herein are methods for identifying nucleic acid sequences that modulate the function of a cell, the expression of a gene in a cell, or the biological activity of a target polypeptide in a cell. The methods involve the use of double stranded RNA expression libraries, double stranded RNA molecules, and post-transcriptional gene silencing techniques.

Post-transcriptional gene silencing using expressed double stranded RNA

The present invention features compounds useful for inhibiting RNase P activity. These compounds can be used as therapeutics for treating or preventing a variety of bacterial infections. The compounds belong to several classes including mono- and bis-guanylhydrazones, guanylhydrazone mimetics, and benzothiazolium compounds. Exemplary compounds are compounds of formula I:Y&#x2014;(NR')&#x2014;U&#x2014;(NR&#x2033;)&#x2014;A&#x2014;(NR)&#x2014;U&#x2014;(NR)&#x2014;Z&#x2003;&#x2003;Iwith substituents as described herein.

Inhibitors of RNase P proteins as antibacterial compounds

The invention features novel RNase P molecules and nucleic acids encoding the same. Methods for discovery of antimicrobial compounds are also featured.

Bacterial RNase P proteins and their use in identifying antibacterial compounds

The invention features compounds that inhibit secretion of a protein encoded by an ARE-mRNA or that modulate regulation of an ARE-mRNA. These compounds are useful for the treatment or prevention of conditions involving proteins encoded by ARE-mRNAs, such as TNF&#x3b1;.

Small molecule inhibitors of secretion of proteins encoded by ARE-mRNAs

Disclosed are nucleic acid sequences which, when present in an RNA molecule, bind to RNA binding proteins. These nucleic acid sequences are present in untranslated regions of certain mRNA. They can be used in assays to identify compounds that affect the interaction of RNA containing the nucleic acid sequence, such as the source mRNA, and RNA binding proteins. The disclosed nucleic acid sequences can also be used to identify RNA binding proteins that can interact with the sequences. An assay for identifying compounds that affect interaction of RNA containing one of the disclosed nucleic acid sequences and RNA binding proteins is also disclosed. The assay involves detecting interactions between RNA binding proteins and an RNA molecule containing one of the disclosed nucleic acid sequences in the presence of a test compound and in the absence of the test compound. A difference in the detected interaction in the presence and absence of the test compound indicates that the compound affects the interaction. The identified compounds can be used to affect the interaction of RNA binding proteins with mRNA containing the nucleic acid sequences or related sequences.

Method for identifying compounds RNA/RNA binding protein interactions

The invention features cDNA libraries consisting essentially of cDNA sequences that correspond to different mRNA untranslated region (UTR) sequences separate from adjacent mRNA coding sequences. The invention also features methods for generating these libraries and for identifying a regulatory UTR sequence.

Functional genomic screen for post-transcriptional 5&prime; and 3&prime; regulatory elements

It has been discovered that a single set of conditions can be used to detect nearly every interaction of RNA binding proteins and RNA molecules. Prior to this discovery it was thought that each specific interaction required separate optimized conditions in order to be detected. Assays employing the disclosed universal conditions are useful for identifying RNA binding proteins that interact with specific RNA molecules of interest, detecting RNA molecules that interact with specific RNA binding proteins of interest, identifying RNA binding proteins active in certain cell types and under certain physiological conditions, identifying specific regions of an RNA molecule that interact with RNA binding proteins. Such assays are useful as a research tool for identifying targets for drug discovery, identifying altered or defective RNA/RBP interactions associated with disease conditions, and in screening assays to identify compounds that modulate RNA/RBP interactions of interest.

Universal method for detecting interactions between RNA molecules and

It has been discovered that a single set of conditions can be used to detect nearly every interaction of RNA binding proteins and RNA molecules. Prior to this discovery it was thought that each specific interaction required separate optimized conditions in order to be detected. Assays employing the disclosed universal conditions are useful for identifying RNA binding proteins that interact with specific RNA molecules of interest, detecting RNA molecules that interact with specific RNA binding proteins of interest, identifying RNA binding proteins active in certain cell types and under certain physiological conditions, identifying specific regions of an RNA molecule that interact with RNA binding proteins. Screening assays employing the disclosed universal conditions are useful for identifying compounds that modulate RNA/RBP interactions of interest.

Method for identifying compounds affecting RNA/RNA binding protein

Disclosed is a method for identifying possible binding sites for RNA binding proteins in nucleic acid sequences, and confirming the identity of such prospective binding sites by detection of interaction between the prospective binding site and RNA binding proteins. Also disclosed are specific binding sites of RNA binding proteins which have been identified using this method.

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Phoenixville, PA, United States of America

Tony Giordano