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Eight RNAi-Related Patent Applications Published by the USPTO: Nov 25, 2005

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Title: RNA Interference Modulators of Hedgehog Signaling and Uses Thereof

Number: 20050256076

Filed: March 24, 2005

Inventor: David Bumcrot, Curis

The patent application, its abstract states, "relates to methods and reagents for modulating the Hedgehog signaling pathway using RNA interference technology. The application provides potential targets of the Hedgehog RNAi, methods to identify additional Hedgehog signaling pathway components, methods to inhibit Hedgehog signaling targets using siRNA, and their uses in the treatment of a number of disease conditions."


Title: Dual-Functional Oligonucleotides for Use in Repressing Mutant Gene Expression

Number: 20050256072

Filed: Feb. 9, 2005

Lead Inventor: Neil Aronin, University of Massachusetts

The invention, the patent application's abstract states, "is based, in part, on the discovery that endogenous mRNAs can be recruited for translational repression of target mRNAs. The RNA-silencing agents and the methods described herein, thereby provide a means by which to treat genetic (e.g., genetic neurodegenerative diseases such as Huntington's disease) or non-genetic diseases by, for example, blocking the synthesis of proteins that contribute to the diseases. Accordingly the RNA-silencing agents of the present invention have an mRNA targeting moiety, a linking moiety, and an mRNA recruiting moiety."


Title: Inhibitor Nucleic Acids

Number: 20050256071

Filed: Jan. 27, 2005

Inventor: Mark Davis, California Institute of Technology (Calando Pharmaceuticals)

According to the patent application's abstract, the invention "provides methods and compositions for attenuating expression of a target gene in vivo. In general, the method includes administering RNAi constructs (such as small-interfering RNAs) that are targeted to particular mRNA sequences, or nucleic acid material that can produce siRNAs in a cell, in an amount sufficient to attenuate expression of a target gene by an RNA interference mechanism. In particular, the RNAi constructs may include one or more modifications to improve serum stability, cellular uptake and/or to avoid non-specific effect," the abstract notes. "In certain embodiments, the RNAi constructs contain an aptamer portion. The aptamer may bind to human serum albumin to improve serum half life. The aptamer may also bind to a cell surface protein that improves uptake of the construct."


Title: iRNA Agents with Biocleavable Tethers

Number: 20050256069

Filed: Nov. 9, 2004

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

"The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group," the patent application's abstract states. "The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent, to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered," the abstract states. "The invention also relates to methods of making and using such modified iRNA agents."


Title: RNA Interference-Mediated Inhibition of Stearoyl-CoA Desaturase Gene Expression Using Short Interfering Nucleic Acid

Number: 20050256068

Filed: Aug. 20, 2004

Lead Inventor: James McSwiggen, Sirna Therapeutics

"This invention relates to compounds, compositions, and methods useful for modulating Stearoyl-CoA desaturase gene expression using short interfering nucleic acid molecules," the patent application's abstract states. "This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of Stearoyl-CoA desaturase gene expression and/or activity by RNA interference using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid, short interfering RNA, double-stranded RNA (dsRNA), microRNA, and short hairpin RNA molecules and methods used to modulate the expression of Stearoyl-CoA desaturase genes."


Title: Methods and Compositions for Selecting siRNA of Improved Functionality

Number: 20050255487

Filed: Sept. 14, 2004

Lead Inventor: Anastasia Khvorova, Dharmacon

"Efficient sequence specific gene silencing is possible through the use of siRNA technology," the patent application's abstract states. "By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed."


Title: Composition and Method for Introduction of DNA-Directed RNA Interference Sequences into Targeted Cells and Tissues

Number: 20050255120

Filed: May 11, 2005

Inventor: Michael Simon, Henry Ford Health System

According to the patent application's abstract, "double-stranded DNA which encodes for a promoter region and for small interfering RNA nucleotide sequences is introduced into specific cells and tissues for the purpose of inhibiting gene expression and protein production in those cells and tissues. Intracellular introduction of the small interfering RNA nucleotide sequences is accomplished by the internalization of a target cell specific ligand bonded to the double-stranded DNA which encodes for a promoter region and for a small interfering RNA nucleotide sequence. The ligand is spontaneously internalized after binding to the cell surface antigen," the abstract states. "Optionally, internalization is also facilitated by the binding of a DNA binding protein to the double-stranded DNA. If the unique cell surface antigen is not naturally internalized after binding to its ligand, internalization is promoted by the incorporation of an internalization moiety into the structure of the ligand or attachment of such a peptide to the ligand."


Title: Nucleic Acid Silencing of Huntington's Disease Gene

Number: 20050255086

Filed: Jan. 31, 2005

Lead Inventor: Beverly Davidson, University of Iowa (Sirna Therapeutics)

The invention, the patent application's abstract states, "is directed to small interfering RNA molecules targeted against a Huntington's disease gene, and methods of using these siRNA molecules."

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