| Methods of inhibiting vegf-c -> Monitor Keywords |
|
|
  Methods of inhibiting vegf-cUSPTO Application #: 20070042986Title: Methods of inhibiting vegf-c Abstract: The present invention provides RNA molecules (e.g., antisense, RNAi, or siRNA) specific for VEGF-C, and further provides methods of reducing expression of VEGF-C in cells (e.g., cancer cells). (end of abstract) Agent: Viksnins Harris & Padys Pllp - St. Paul, MN, US Inventors: Douglas K. Trask, Jonathan Bock USPTO Applicaton #: 20070042986 - Class: 514044000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), O-glycoside, , Nitrogen Containing Hetero Ring, Polynucleotide (e.g., Rna, Dna, Etc.) The Patent Description & Claims data below is from USPTO Patent Application 20070042986. Brief Patent Description - Full Patent Description - Patent Application Claims
CLAIM OF PRIORITY [0001] This patent application is a Divisional Application of U.S. application Ser. No. 11/194,276 filed on Aug. 1, 2005, which claims priority to U.S. application Ser. No. 60/598,003 filed on Aug. 2, 2004. The instant application claims the benefit of the listed applications, which are hereby incorporated by reference herein in their entirety. TECHNICAL FIELD [0002] This invention relates to siRNA molecules, and more particularly to VEGF-C siRNA molecules. BACKGROUND [0003] Vascular endothelial growth factor C (VEGF-C; also known as vascular permeability factor) is a member of the signaling growth factor family. VEGF-C is a growth factor active in angiogenesis and endothelial cell growth, and stimulates their proliferation and migration. VEGF-C also has effects on the permeability of blood vessels. VEGF-C may function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. VEGF-C generally has several cysteine-rich motifs, and usually is about 47 kDa. VEGF-C is expressed in the spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine, fetal liver, fetal lung, and fetal kidney. SUMMARY [0004] The present invention provides RNA molecules (e.g., antisense, RNAi, or siRNA) specific for VEGF-C, and further provides methods of reducing expression of VEGF-C in a cell (e.g., a cancer cell). [0005] In one aspect, the invention provides an isolated nucleic acid molecule having a first portion. Generally, the first portion is no more than 30 nucleotides in length, and includes the sequence 5'-AAG ATC TGG AGG AGC AGT TAC-3' (SEQ ID NO: 1), 5'AAA GGA GGC TGG CAA CAT AAC-3' (SEQ ID NO:2), 5'-AAC CTC CAT GTT GTG TCC GTC-3' (SEQ ID NO:3), 5'-AAG ACC TGC CCC ACC AAT TAC-3' (SEQ ID NO:4), or 5'-AAG AAG TGT GTC GTT GTG TCC-3' (SEQ ID NO:5). [0006] In another aspect, the invention provides methods of reducing the expression of VEGF-C in a cell. Such methods include introducing an isolated nucleic acid molecule in to the cell in an amount sufficient to reduce the expression of VEGF-C. Generally, the nucleic acid molecule has a first portion that is no more than 30 nucleotides in length. The first portion typically includes the sequence 5'-AAG ATC TGG AGG AGC AGT TAC-3' (SEQ ID NO:1), 5'-AAA GGA GGC TGG CAA CAT AAC-3' (SEQ ID NO:2), 5'-AAC CTC CAT GTT GTG TCC GTC-3' (SEQ ID NO:3), 5'-AAG ACC TGC CCC ACC AAT TAC-3' (SEQ ID NO:4), or 5'-AAG AAG TGT GTC GTT GTG TCC-3' (SEQ ID NO:5). According to the invention, the nucleic acid molecule reduces expression of VEGF-C in the cell. VEGF-C expression can be reduced by at least 10%. [0007] The nucleic acid molecules described above also can include a second portion having a sequence complementary to the first portion. Such nucleic acid molecules further can include a linking sequence that joins the first portion and the second portion. For example, the linking sequence can form a loop of a hairpin. Typically, the linking sequence is about 4 to about 10 nucleotides in length, and the first portion is from 19 to 23 nucleotides in length. The invention also provides for vectors containing such nucleic acid molecules, as well as host cells containing such vectors. [0008] A representative cell in which VEGF-C expression can be reduced is a cancer cell. Such cancer cells can be epithelially-derived, and can include, for example, a head and neck cancer cell, a breast cancer cell, a colon cancer cell, and a prostate cancer cell. In various embodiments, the cancer cell is in vivo; the cancer cell is in a mammal (e.g., a human). It is a feature of the invention that proliferation of the cancer cell is inhibited. [0009] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. [0010] The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the drawings and detailed description, and from the claims. DESCRIPTION OF DRAWINGS [0011] FIG. 1 is a graph showing the results of quantitative RT-PCR of VEGF-C expression in head and neck cancer cells transfected with a VEGF-C siRNA. [0012] Like reference symbols in the various drawings indicate like elements. DETAILED DESCRIPTION [0013] Several RNA molecules have been identified that are specific for VEGF-C and that can selectively reduce expression of VEGF-C in a cell. The invention provides for such VEGF-C RNA molecules, the DNA molecules encoding such RNA molecules, and also provides for methods of using the nucleic acid molecules of the invention to reduce the expression of VEGF-C. The RNA molecules of the invention can be used in a number of different forms including antisense, RNAi, and siRNA. Although the following discussion focuses on siRNA, the methods of the invention are not limited by a particular mechanism. VEGF-C siRNA Molecules [0014] A "small interfering RNA" or "short interfering RNA" or "siRNA" or "short hairpin RNA" or "shRNA" is a double-stranded RNA molecule that is complementary to a target nucleic acid sequence, for example, VEGF-C. A double-stranded RNA molecule is formed by the complementary pairing between a first RNA portion and a second RNA portion. The length of each portion generally is less than 30 nucleotides in length (e.g., 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, or 10 nucleotides). In some embodiments, the length of each portion is 19 to 25 nucleotides in length. In some siRNA molecules, the complementary first and second portions of the RNA molecule are the "stem" of a hairpin structure. The two portions can be joined by a linking sequence, which can form the "loop" in the hairpin structure. The linking sequence can vary in length. In some embodiments, the linking sequence can be 5, 6, 7, 8, 9, 10, 11, 12 or 13 nucleotides in length. A representative linking sequence is 5'-TTC AGA AGG-3', but any of a number of sequences can be used to join the first and second portions. The first and second portions are complementary but may not be completely symmetrical, as the hairpin structure may contain 3' or 5' overhang nucleotides (e.g., a 1, 2, 3, 4, or 5 nucleotide overhang). [0015] RNA molecules have been shown by many researchers to be effective in suppressing mRNA accumulation. siRNA-mediated suppression of nucleic acid expression is specific as even a single base pair mismatch between siRNA and the targeted nucleic acid can abolish the action of RNA interference. siRNAs generally do not elicit anti-viral responses. [0016] There are well-established criteria for designing siRNAs (see, e.g., Elbashire et al., 2001, Nature, 411:494-8; Amarzguioui et al., 2004, Biochem. Biophys. Res. Commun., 316(4):1050-8; Reynolds et al., 2004, Nat. Biotech., 22(3):326-30). Details can be found in the websites of several commercial vendors such as Ambion, Dharmacon, GenScript, and OligoEngine. The sequence of any potential siRNA candidate generally is checked for any possible matches to other nucleic acid sequences or polymorphisms of nucleic acid sequence using the BLAST alignment program (see ncbi.nlm.nih.gov on the World Wide Web). Typically, a number of siRNAs have to be generated and screened in order to compare their effectiveness. [0017] Once designed, the siRNAs of the present invention can be generated by any method known in the art, for example, by in vitro transcription, recombinantly, or by synthetic means (e.g., having either a TT or a UU overhang at the 3' end). siRNAs can be generated in vitro by using a recombinant enzyme, such as T7 RNA polymerase, and DNA oligonucleotide templates, or can be prepared in vivo, for example, in cultured cells (see, for example, Elbashir et al., supra; Brummelkamp et al., supra; and Lee et al., 2002, Nat. Biotech., 20:500-5). Continue reading... Full patent description for Methods of inhibiting vegf-c Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Methods of inhibiting vegf-c patent application. Patent Applications in related categories: 20080108584 - Compositions and methods for inhibiting expression of ikk-b gene - The invention relates to a doable-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the ... 20080108585 - Dna vaccination for treatment of autoimmune disease - A pro-inflammatory T cell response is specifically suppressed by the injection into a recipient of DNA encoding an autoantigen associated with autoimmune disease. The recipient may be further treating by co-vaccination with a DNA encoding a Th2 cytokine, particularly encoding IL4. In response to the vaccination, the proliferation of autoantigen-reactive ... 20080108583 - Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes - The invention relates to one or more inhibitors, in particular siRNAs, which down-regulate the expression of human pro-apoptotic genes. The invention also relates to a pharmaceutical composition comprising the compound, or a vector capable of expressing the compound, and a pharmaceutically acceptable carrier. The present invention also contemplates a method ... ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Methods of inhibiting vegf-c or other areas of interest. ### Previous Patent Application: Gp131: methods and compositions for treating cancer Next Patent Application: Nf-hev compositions and methods of use Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Methods of inhibiting vegf-c patent info. IP-related news and info Results in 3.07601 seconds Other interesting Feshpatents.com categories: Daimler Chrysler , DirecTV , Exxonmobil Chemical Company , Goodyear , Intel , Kyocera Wireless , |
||
