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Eight RNAi-Related Patent Applications Published by the US Patent Office

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Title: Methods and Compositions for Inhibiting the Function of Polynucleotide Sequences. Number: 20040266721. Filed: July 22, 2004. Lead Inventor: Chandrasekhar Satishchandran, Wyeth (Nucleonics).

According to the patent application’s abstract, the invention is a “therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell [and] includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein,” the abstract notes. “The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro, or made in recombinant cultures of microorganisms and isolated therefrom; or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell. In methods of treatment of prophylaxis of virus infections, other pathogenic infections or certain cancers, these compositions are administered in amounts effective to reduce or inhibit the function of the target polynucleotide sequence, which can be of pathogenic origin or produced in response to a tumor or other cancer, among other sources,” it adds.


Title: Stabilized Polynucleotides for Use in RNA Interference. Number: 20040266707. Filed: July 1, 2003. Lead Inventor: Devin Leake, Dharmacon.

“Methods and compositions for performing RNA interference comprising a wide variety of stabilized polynucleotides suitable for use in serum-containing media and for in vivo applications, such as therapeutic applications, are provided” by the patent application, its abstract states. “These polynucleotides permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of one or more modifications including orthoesters, terminal conjugates, modified linkages, and 2’-modified nucleotides.”


Title: Cross-Linked Oligomeric Compounds and Their Use In Gene Modulation. Number: 20040266706. Filed: June 26, 2003. Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals.

“The present invention provides modified oligomeric compounds that modulate gene expression via an RNA interference pathway,” the patent application’s abstract states. “The oligomeric compounds of the invention include one or more cross-linkages that can improve nuclease resistance or modify or enhance the pharmacokinetic and phamacodynamic properties of the oligomeric compound.”


Title: RNA Interference Pathway Genes as Tools for Targeted Genetic Interference. Number: 20040265839. Filed: Aug. 20, 2003. Lead Inventor: Craig Mello, University of Massachusetts Medical School.

According to the patent application’s abstract, “genes involved in double-stranded RNA interference (RNAi pathway genes) are identified and used to investigate the RNAi pathway. The genes and their products are also useful for modulating RNAi pathway activity.”


Title: SiRNA-Mediated Inhibition of Gene Expression in Plant Cells. Number: 20040261149. Filed: Feb. 24, 2004. Lead Inventor: Claude Fauquet, Donald Danforth Plant Science Center.

“The … invention relates to short-interfering RNAs and methods of using the same to suppress or inhibit gene expression in plant cells,” the patent application’s abstract states. “In particular, the present invention relates to siRNAs and methods that can be used to suppress or inhibit viral gene expression in plant cells. Still more particularly, the present invention relates to siRNAs and methods that can be used to suppress or inhibit geminiviral gene expression in plant cells. Of course, the siRNAs of the present invention could be used to generate plants that are resistant to geminiviral infection,” the abstract notes. “In addition, methods of identifying specific compositions, or siRNAs, that can be used to inhibit gene expression in plant cells generally are provided.”


Title: RNA Interference-Mediating Small RNA Molecules. Number: 20040259248. Filed: April 27, 2004. Lead Inventor: Thomas Tuschl, Max Planck Institute.

According to the patent application’s abstract, the invention comprises “double-stranded RNA [that induce] sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference. Using a Drosophila in vitro system, we demonstrate that 19-23 [nucleotide]-short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3’ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA,” the abstract states. “Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.”


Title: RNA Interference-Mediating Small RNA Molecules. Number: 20040259247. Filed: July 26, 2004. PCT Filed: Nov. 29, 2001. Lead Inventor: Thomas Tuschl, Max Planck Institute.

“Double-stranded RNA induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi),” the patent application states. “Using a Drosophila in vitro system, we demonstrate that 19-23 [nucleotide]-short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs are generated by an RNase III-like processing reaction from long dsRNA,” it adds. “Chemically synthesized siRNA duplexes with overhanging 3’ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.”


Title: Method for the In Vitro Synthesis of Short Double-Stranded RNAs. Number: 20040259097. Filed: May 4, 2004. PCT Filed: Oct. 30, 2002. Lead Inventor: Marianne Denise De Backer, Johnson & Johnson.

“The … invention relates to the field of synthesis of short double-stranded RNAs,” the patent application’s abstract states. “An in vitro transcription method using bacteriophage polymerases and target sequence-specific single-stranded DNA oligonucleotides as templates is disclosed. The present invention finds particularly advantageous use in the synthesis of short interfering RNAs that have been shown to function as key intermediates in triggering sequence-specific RNA degradation during posttranscriptional gene silencing in plants and RNA interference in invertebrates and vertebrate systems.”

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