WO2003070918A3 - Rna interference by modified short interfering nucleic acid - Google Patents

Rna interference by modified short interfering nucleic acid Download PDF

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Publication number
WO2003070918A3
WO2003070918A3 PCT/US2003/005346 US0305346W WO03070918A3 WO 2003070918 A3 WO2003070918 A3 WO 2003070918A3 US 0305346 W US0305346 W US 0305346W WO 03070918 A3 WO03070918 A3 WO 03070918A3
Authority
WO
WIPO (PCT)
Prior art keywords
nucleic acid
rna
short interfering
rna interference
interfering nucleic
Prior art date
Application number
PCT/US2003/005346
Other languages
French (fr)
Other versions
WO2003070918A2 (en
Inventor
James Mcswiggen
Leonid Beigelman
Dennis Macejak
Shawn Zinnen
Pamela Pavco
David Morrissey
Kathy Fosnaugh
Victor Mokler
Sharon Jamison
Original Assignee
Ribozyme Pharm Inc
James Mcswiggen
Leonid Beigelman
Dennis Macejak
Shawn Zinnen
Pamela Pavco
David Morrissey
Kathy Fosnaugh
Victor Mokler
Sharon Jamison
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ribozyme Pharm Inc, James Mcswiggen, Leonid Beigelman, Dennis Macejak, Shawn Zinnen, Pamela Pavco, David Morrissey, Kathy Fosnaugh, Victor Mokler, Sharon Jamison filed Critical Ribozyme Pharm Inc
Priority to JP2003569811A priority Critical patent/JP2005517438A/en
Priority to CA002459532A priority patent/CA2459532A1/en
Priority to GB0406022A priority patent/GB2397818B/en
Priority to AU2003221258A priority patent/AU2003221258B2/en
Priority to EP03716126A priority patent/EP1458741B1/en
Priority to US10/424,339 priority patent/US20060127891A1/en
Priority to US10/427,160 priority patent/US7833992B2/en
Priority to US10/444,853 priority patent/US8202979B2/en
Priority to PCT/US2003/018911 priority patent/WO2003106476A1/en
Priority to US10/607,933 priority patent/US20080032942A1/en
Publication of WO2003070918A2 publication Critical patent/WO2003070918A2/en
Priority to US10/652,791 priority patent/US20050106726A1/en
Priority to US10/693,059 priority patent/US20080039414A1/en
Priority to US10/720,448 priority patent/US8273866B2/en
Priority to US10/724,270 priority patent/US20050080031A1/en
Priority to US10/727,780 priority patent/US20050233329A1/en
Priority to US10/757,803 priority patent/US20050020525A1/en
Priority to US10/780,447 priority patent/US7491805B2/en
Priority to US10/783,128 priority patent/US20050096284A1/en
Priority to US10/798,090 priority patent/US20050014172A1/en
Priority to US10/800,487 priority patent/US20050048529A1/en
Priority to US10/824,036 priority patent/US20050191638A1/en
Priority to US10/825,485 priority patent/US20060160757A1/en
Priority to US10/826,966 priority patent/US20050032733A1/en
Priority to US10/831,620 priority patent/US20050148530A1/en
Priority to US10/830,569 priority patent/US20050054598A1/en
Priority to US10/832,522 priority patent/US20050233996A1/en
Priority to US10/840,731 priority patent/US20050137153A1/en
Priority to US10/844,076 priority patent/US7176304B2/en
Priority to US10/844,072 priority patent/US20050159376A1/en
Priority to US10/557,542 priority patent/US20070032441A1/en
Priority to US10/861,060 priority patent/US20050137155A1/en
Priority to US10/864,044 priority patent/US20050171040A1/en
Priority to US10/863,973 priority patent/US20050143333A1/en
Priority to US10/869,638 priority patent/US20050119211A1/en
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Priority to US10/562,561 priority patent/US20060247194A1/en
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Priority to US10/881,580 priority patent/US20060142225A1/en
Priority to US10/881,118 priority patent/US20050130181A1/en
Priority to US10/883,218 priority patent/US20050124567A1/en
Publication of WO2003070918A3 publication Critical patent/WO2003070918A3/en
Priority to US10/888,269 priority patent/US20050222064A1/en
Priority to US10/888,226 priority patent/US20050124568A1/en
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8216Methods for controlling, regulating or enhancing expression of transgenes in plant cells
    • C12N15/8218Antisense, co-suppression, viral induced gene silencing [VIGS], post-transcriptional induced gene silencing [PTGS]
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    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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Abstract

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.
PCT/US2003/005346 2000-02-11 2003-02-20 Rna interference by modified short interfering nucleic acid WO2003070918A2 (en)

Priority Applications (231)

Application Number Priority Date Filing Date Title
JP2003569811A JP2005517438A (en) 2002-02-20 2003-02-20 RNA interference-mediated inhibition of gene expression using chemically modified short interfering nucleic acids (siNA)
CA002459532A CA2459532A1 (en) 2002-02-20 2003-02-20 Rna interference by modified short interfering nucleic acid
GB0406022A GB2397818B (en) 2002-02-20 2003-02-20 Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
AU2003221258A AU2003221258B2 (en) 2002-02-20 2003-02-20 RNA interference by modified short interfering nucleic acid
EP03716126A EP1458741B1 (en) 2002-02-20 2003-02-20 Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
US10/424,339 US20060127891A1 (en) 2002-02-20 2003-04-25 RNA interference mediated inhibition of MAP kinase gene expression or expression of genes involved in MAP kinase pathway using short interfering nucleic acid (siNA)
US10/427,160 US7833992B2 (en) 2001-05-18 2003-04-30 Conjugates and compositions for cellular delivery
US10/444,853 US8202979B2 (en) 2002-02-20 2003-05-23 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
PCT/US2003/018911 WO2003106476A1 (en) 2002-02-20 2003-06-16 Nucleic acid mediated inhibition of enterococcus infection and cytolysin toxin activity
US10/607,933 US20080032942A1 (en) 2000-08-30 2003-06-27 RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA)
US10/652,791 US20050106726A1 (en) 2002-02-20 2003-08-29 RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US10/693,059 US20080039414A1 (en) 2002-02-20 2003-10-23 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US10/720,448 US8273866B2 (en) 2002-02-20 2003-11-24 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA)
US10/724,270 US20050080031A1 (en) 2001-05-18 2003-11-26 Nucleic acid treatment of diseases or conditions related to levels of Ras, HER2 and HIV
US10/727,780 US20050233329A1 (en) 2002-02-20 2003-12-03 Inhibition of gene expression using duplex forming oligonucleotides
US10/757,803 US20050020525A1 (en) 2002-02-20 2004-01-14 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US10/780,447 US7491805B2 (en) 2001-05-18 2004-02-13 Conjugates and compositions for cellular delivery
US10/783,128 US20050096284A1 (en) 2002-02-20 2004-02-20 RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US10/798,090 US20050014172A1 (en) 2002-02-20 2004-03-11 RNA interference mediated inhibition of muscarinic cholinergic receptor gene expression using short interfering nucleic acid (siNA)
US10/800,487 US20050048529A1 (en) 2002-02-20 2004-03-15 RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA)
US10/824,036 US20050191638A1 (en) 2002-02-20 2004-04-14 RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US10/825,485 US20060160757A1 (en) 2002-02-20 2004-04-15 RNA interference mediated inhibition hairless of (HR) gene expression using short interfering nucleic acid (siNA)
US10/826,966 US20050032733A1 (en) 2001-05-18 2004-04-16 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
US10/831,620 US20050148530A1 (en) 2002-02-20 2004-04-23 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US10/830,569 US20050054598A1 (en) 2002-02-20 2004-04-23 RNA interference mediated inhibition hairless (HR) gene expression using short interfering nucleic acid (siNA)
US10/832,522 US20050233996A1 (en) 2002-02-20 2004-04-26 RNA interference mediated inhibition of hairless (HR) gene expression using short interfering nucleic acid (siNA)
US10/840,731 US20050137153A1 (en) 2002-02-20 2004-05-06 RNA interference mediated inhibition of alpha-1 antitrypsin (AAT) gene expression using short interfering nucleic acid (siNA)
US10/844,076 US7176304B2 (en) 2002-02-20 2004-05-11 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US10/844,072 US20050159376A1 (en) 2002-02-20 2004-05-12 RNA interference mediated inhibition 5-alpha reductase and androgen receptor gene expression using short interfering nucleic acid (siNA)
US10/557,542 US20070032441A1 (en) 2001-05-18 2004-05-24 Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina)
US10/861,060 US20050137155A1 (en) 2001-05-18 2004-06-03 RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA)
US10/864,044 US20050171040A1 (en) 2001-05-18 2004-06-09 RNA interference mediated inhibition of cholesteryl ester transfer protein (CEPT) gene expression using short interfering nucleic acid (siNA)
US10/863,973 US20050143333A1 (en) 2001-05-18 2004-06-09 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US10/869,638 US20050119211A1 (en) 2001-05-18 2004-06-16 RNA mediated inhibition connexin gene expression using short interfering nucleic acid (siNA)
US10/871,222 US20050119212A1 (en) 2001-05-18 2004-06-18 RNA interference mediated inhibition of FAS and FASL gene expression using short interfering nucleic acid (siNA)
US10/562,561 US20060247194A1 (en) 2000-08-30 2004-06-25 Rna interference mediated treatment of alzheimer's disease using short interfering nucleic acid (sina)
US10/877,889 US20050209179A1 (en) 2000-08-30 2004-06-25 RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA)
US10/879,867 US20050124566A1 (en) 2001-05-18 2004-06-28 RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA)
US10/881,580 US20060142225A1 (en) 2001-05-18 2004-06-30 RNA interference mediated inhibition of cyclin dependent kinase-2 (CDK2) gene expression using short interfering nucleic acid (siNA)
US10/881,118 US20050130181A1 (en) 2001-05-18 2004-06-30 RNA interference mediated inhibition of wingless gene expression using short interfering nucleic acid (siNA)
US10/883,218 US20050124567A1 (en) 2001-05-18 2004-07-01 RNA interference mediated inhibition of TRPM7 gene expression using short interfering nucleic acid (siNA)
US10/888,269 US20050222064A1 (en) 2002-02-20 2004-07-09 Polycationic compositions for cellular delivery of polynucleotides
US10/888,226 US20050124568A1 (en) 2001-05-18 2004-07-09 RNA interference mediated inhibition of acetyl-CoA-carboxylase gene expression using short interfering nucleic acid (siNA)
US10/893,010 US20050164224A1 (en) 2001-05-18 2004-07-16 RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA)
US10/892,922 US20050124569A1 (en) 2001-05-18 2004-07-16 RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA)
US10/894,475 US20050070497A1 (en) 2001-05-18 2004-07-19 RNA interference mediated inhibtion of tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US10/898,660 US20050196765A1 (en) 2001-05-18 2004-07-23 RNA interference mediated inhibition of checkpoint Kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US10/898,311 US20050277608A1 (en) 2001-05-18 2004-07-23 RNA interference mediated inhibtion of vitamin D receptor gene expression using short interfering nucleic acid (siNA)
US10/897,902 US20050176663A1 (en) 2001-05-18 2004-07-23 RNA interference mediated inhibition of protein tyrosine phosphatase type IVA (PRL3) gene expression using short interfering nucleic acid (siNA)
US10/903,128 US20050182006A1 (en) 2001-05-18 2004-07-30 RNA interference mediated inhibition of protein kinase C alpha (PKC-alpha) gene expression using short interfering nucleic acid (siNA)
US10/567,888 US20070093437A1 (en) 2001-05-18 2004-08-06 Rna interference mediated inhibition of xiap gene expression using short interfering nucleic acid (sina)
US10/916,095 US20050158735A1 (en) 2001-05-18 2004-08-11 RNA interference mediated inhibition of proliferating cell nuclear antigen (PCNA) gene expression using short interfering nucleic acid (siNA)
US10/915,896 US20050159378A1 (en) 2001-05-18 2004-08-11 RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA)
US10/916,030 US20050159379A1 (en) 2001-05-18 2004-08-11 RNA interference mediated inhibition of gastric inhibitory polypeptide (GIP) and gastric inhibitory polypeptide receptor (GIPR) gene expression using short interfering nucleic acid (siNA)
US10/918,987 US20050203040A1 (en) 2001-05-18 2004-08-16 RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US10/918,969 US20050153914A1 (en) 2001-05-18 2004-08-16 RNA interference mediated inhibition of MDR P-glycoprotein gene expression using short interfering nucleic acid (siNA)
US10/918,896 US20050164966A1 (en) 2001-05-18 2004-08-16 RNA interference mediated inhibition of type 1 insulin-like growth factor receptor gene expression using short interfering nucleic acid (siNA)
US10/919,964 US20050176665A1 (en) 2001-05-18 2004-08-17 RNA interference mediated inhibition of hairless (HR) gene expression using short interfering nucleic acid (siNA)
US10/919,584 US20050233997A1 (en) 2001-05-18 2004-08-17 RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
US10/919,866 US20050176664A1 (en) 2001-05-18 2004-08-17 RNA interference mediated inhibition of cholinergic muscarinic receptor (CHRM3) gene expression using short interfering nucleic acid (siNA)
US10/922,034 US20050164967A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US10/923,640 US20050136436A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of G72 and D-amino acid oxidase (DAAO) gene expression using short interfering nucleic acid (siNA)
US10/923,580 US20050159382A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA)
US10/922,626 US20050159380A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of angiopoietin gene expression using short interfering nucleic acid (siNA)
US10/922,544 US20050153915A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of early growth response gene expression using short interfering nucleic acid (siNA)
US10/921,554 US20060142226A1 (en) 2001-05-18 2004-08-19 RNA interference mediated inhibition of cholesteryl ester transfer protein (CETP) gene expression using short interfering nucleic acid (siNA)
US10/923,379 US20050239731A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of MAP kinase gene expression using short interfering nucleic acid (siNA)
US10/923,536 US20070042983A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US10/923,330 US20050153916A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of telomerase gene expression using short interfering nucleic acid (siNA)
US10/923,516 US20050176025A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA)
US10/923,522 US20050159381A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of chromosome translocation gene expression using short interfering nucleic acid (siNA)
US10/922,675 US20050182007A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US10/923,270 US20050233344A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of platelet derived growth factor (PDGF) and platelet derived growth factor receptor (PDGFR) gene expression using short interfering nucleic acid (siNA)
US10/922,761 US20050267058A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (sINA)
US10/923,470 US20050227935A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of TNF and TNF receptor gene expression using short interfering nucleic acid (siNA)
US10/923,201 US20050182009A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of NF-Kappa B / REL-A gene expression using short interfering nucleic acid (siNA)
US10/923,451 US20050256068A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of stearoyl-CoA desaturase (SCD) gene expression using short interfering nucleic acid (siNA)
US10/923,476 US20050288242A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA)
US10/923,182 US20050176666A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of GPRA and AAA1 gene expression using short interfering nucleic acid (siNA)
US10/923,473 US20050191618A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA)
US10/923,475 US20050227936A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
US10/923,181 US20050187174A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA)
US10/923,115 US20050079610A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA)
US10/923,354 US20050176024A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of epidermal growth factor receptor (EGFR) gene expression using short interfering nucleic acid (siNA)
US10/923,142 US20050182008A1 (en) 2000-02-11 2004-08-20 RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA)
US10/923,329 US20050164968A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of ADAM33 gene expression using short interfering nucleic acid (siNA)
US10/923,380 US20050196767A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA)
US10/922,340 US20050170371A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of 5-alpha reductase and androgen receptor gene expression using short interfering nucleic acid (siNA)
US10/922,554 US20080188430A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA)
US10/942,560 US20050209180A1 (en) 2001-05-18 2004-09-15 RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA)
US10/944,611 US20050233998A1 (en) 2001-05-18 2004-09-16 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US10/962,898 US20050222066A1 (en) 2001-05-18 2004-10-12 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
HK04107996.5A HK1065049A1 (en) 2002-02-20 2004-10-15 Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
US10/981,966 US20050266422A1 (en) 2002-02-20 2004-11-05 Fluoroalkoxy, nucleosides, nucleotides, and polynucleotides
US11/001,347 US20050261219A1 (en) 2001-05-18 2004-12-01 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US11/011,913 US20050209182A1 (en) 2002-02-20 2004-12-14 Nucleic acid mediated inhibition of enterococcus infection and cytolysin toxin activity
US11/014,373 US20050196781A1 (en) 2001-05-18 2004-12-15 RNA interference mediated inhibition of STAT3 gene expression using short interfering nucleic acid (siNA)
US11/031,668 US20060019913A1 (en) 2001-05-18 2005-01-06 RNA interference mediated inhibtion of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US11/035,813 US20060025361A1 (en) 2001-05-18 2005-01-14 RNA interference mediated inhibition of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US11/054,047 US20050287128A1 (en) 2001-05-18 2005-02-09 RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
US11/058,582 US20050260620A1 (en) 2001-05-18 2005-02-15 RNA interference mediated inhibition of retinolblastoma (RBI) gene expression using short interfering nucleic acid (siNA)
US11/063,415 US20050277133A1 (en) 2001-05-18 2005-02-22 RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US11/098,303 US20050282188A1 (en) 2001-05-18 2005-04-04 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US11/140,328 US20060019917A1 (en) 2001-05-18 2005-05-27 RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA)
US11/205,646 US20080161256A1 (en) 2001-05-18 2005-08-17 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US11/217,936 US20060148743A1 (en) 2001-05-18 2005-09-01 RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA)
US11/234,730 US20070270579A1 (en) 2001-05-18 2005-09-23 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US11/259,603 US20060241075A1 (en) 2001-05-18 2005-10-26 RNA interference mediated inhibition of desmoglein gene expression using short interfering nucleic acid (siNA)
US11/265,730 US20070179104A1 (en) 2001-05-18 2005-11-02 RNA interference mediated inhibition of winged helix nude (WHN) gene expression using short interfering nucleic acid (siNA)
US11/299,254 US20060217331A1 (en) 2001-05-18 2005-12-08 Chemically modified double stranded nucleic acid molecules that mediate RNA interference
US11/299,391 US7517864B2 (en) 2001-05-18 2005-12-09 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US11/311,826 US20060211642A1 (en) 2001-05-18 2005-12-19 RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
US11/332,655 US20060276422A1 (en) 2001-05-18 2006-01-13 RNA interference mediated inhibition of B7-H1 gene expression using short interfering nucleic acid (siNA)
US11/358,807 US20060217335A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,932 US20060217337A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,862 US20060287266A1 (en) 2002-02-20 2006-02-21 RNA interference mediated ihibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,443 US20060217334A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,540 US20060247428A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,924 US20060247429A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/358,863 US20060217336A1 (en) 2002-02-20 2006-02-21 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/369,108 US20070160980A1 (en) 2001-05-18 2006-03-06 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US11/395,833 US20060287267A1 (en) 2001-05-18 2006-03-31 RNA interference mediated inhibition of respiratory syncytial virus (RSV) expression using short interfering nucleic acid (siNA)
US11/448,115 US20060216747A1 (en) 2001-05-18 2006-06-06 RNA interference mediated inhibition of checkpoint kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US11/450,856 US20060270623A1 (en) 2001-05-18 2006-06-09 RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US11/455,205 US20070049543A1 (en) 2001-05-18 2006-06-16 RNA interference mediated inhibition of 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD-1) gene expression using short interfering nucleic acid siNA
US11/487,788 US20070173473A1 (en) 2001-05-18 2006-07-17 RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US11/488,374 US20080249040A1 (en) 2001-05-18 2006-07-18 RNA interference mediated inhibition of sterol regulatory element binding protein 1 (SREBP1) gene expression using short interfering nucleic acid (siNA)
US11/499,521 US7989612B2 (en) 2002-02-20 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/499,533 US20060293272A1 (en) 2002-02-20 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/499,828 US7956176B2 (en) 2002-09-05 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/499,529 US7923547B2 (en) 2002-09-05 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/499,633 US20070004665A1 (en) 2002-02-20 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/499,520 US20070004663A1 (en) 2002-02-20 2006-08-04 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/502,876 US20060281175A1 (en) 2002-02-20 2006-08-11 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/502,875 US20070004667A1 (en) 2002-02-20 2006-08-11 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/502,885 US20060292691A1 (en) 2002-02-20 2006-08-11 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/502,893 US20060275903A1 (en) 2002-02-20 2006-08-11 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/592,039 US20070185049A1 (en) 2001-05-18 2006-11-02 RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA)
US11/676,124 US8846894B2 (en) 2002-02-20 2007-02-16 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US11/684,465 US20070161596A1 (en) 2000-08-30 2007-03-09 RNA INTERFERENCE MEDIATED TREATMENT OF ALZHEIMER'S DISEASE USING SHORT INTERFERING NUCLEIC ACID (siNA)
US11/748,029 US20090239931A1 (en) 2001-05-18 2007-05-14 RNA INTERFERENCE MEDIATED INHIBITION OF PROTEIN TYROSINE PHOSPHATASE-1B (PTP-1B) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US11/756,240 US20090299045A1 (en) 2001-05-18 2007-05-31 RNA Interference Mediated Inhibition Of Interleukin and Interleukin Gene Expression Using Short Interfering Nucleic Acid (siNA)
US11/879,470 US20080033156A1 (en) 2002-02-20 2007-07-17 Polycationic compositions for cellular delivery of polynucleotides
US11/851,090 US20080249294A1 (en) 2001-05-18 2007-09-06 RNA Interference Mediated Inhibition of Gene Expression Using Short Interfering Nucleic Acid (siNA)
US12/105,010 US8232383B2 (en) 2002-02-20 2008-04-17 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US12/166,991 US20090137507A1 (en) 2002-02-20 2008-07-02 RNA INTERFERENCE MEDIATED INHIBITION OF ANGIOPOIETIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/167,012 US7928218B2 (en) 2002-02-20 2008-07-02 RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA)
US12/167,045 US20090137509A1 (en) 2002-02-20 2008-07-02 RNA INTERFERENCE MEDIATED INHIBITION OF PROLIFERATION CELL NUCLEAR ANTIGEN (PCNA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/169,519 US20090156533A1 (en) 2001-05-18 2008-07-08 RNA INTERFERENCE MEDIATED INHIBITION OF STROMAL CELL-DERIVED FACTOR-1 (SDF-1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/170,310 US7897752B2 (en) 2002-02-20 2008-07-09 RNA interference mediated inhibition of telomerase gene expression using short interfering nucleic acid (siNA)
US12/170,290 US7662951B2 (en) 2000-08-30 2008-07-09 RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA)
US12/171,034 US20090137510A1 (en) 2002-02-20 2008-07-10 RNA INTERFERENCE MEDIATED INHIBITION OF NF-KAPPA B/ REL-A GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/171,111 US7928219B2 (en) 2002-02-20 2008-07-10 RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (SINA)
US12/174,526 US7691999B2 (en) 2002-02-20 2008-07-16 RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA)
US12/175,367 US7795422B2 (en) 2002-02-20 2008-07-17 RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA)
US12/175,385 US7659389B2 (en) 2001-05-18 2008-07-17 RNA interference mediated inhibition of MYC and/or MYB gene expression using short interfering nucleic acid (siNA)
US12/175,392 US20090192105A1 (en) 2002-02-20 2008-07-17 RNA INTERFERENCE MEDIATED INHIBITION OF INTERCELLULAR ADHESION MOLECULE (ICAM) GENE EXPRESSION USING SHORT INTERFERING NUCELIC ACID (siNA)
US12/185,678 US20090099117A1 (en) 2002-02-20 2008-08-04 RNA INTERFERENCE MEDIATED INHIBITION OF MYOSTATIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/185,652 US7910724B2 (en) 2002-02-20 2008-08-04 RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA)
US12/192,853 US8017761B2 (en) 2001-05-18 2008-08-15 RNA interference mediated inhibition of Stearoyl-CoA desaturase (SCD) gene expression using short interfering nucelic acid (siNA)
US12/192,878 US20090247613A1 (en) 2002-02-20 2008-08-15 RNA INTERFERENCE MEDIATED INHIBITION OF B-CELL CLL/LYMPHOMA-2 (BCL2) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/192,869 US20090099119A1 (en) 2001-05-18 2008-08-15 RNA INTERFERENCE MEDIATED INHIBITION OF RAS GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/200,750 US20090137513A1 (en) 2002-02-20 2008-08-28 RNA Interference Mediated Inhibition of Acetyl-CoA-Carboxylase Gene Expression Using Short Interfering Nucleic Acid (siNA)
US12/200,736 US8067575B2 (en) 2002-02-20 2008-08-28 RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA)
US12/201,759 US20090023676A1 (en) 2002-02-20 2008-08-29 RNA Interference Mediated Inhibition of MAP Kinase Gene Expression or Expression of Genes Involved in MAP Kinase Pathway Using Short Interfering Nucleic Acid (SiNA)
US12/203,055 US7700760B2 (en) 2002-02-20 2008-09-02 RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US12/203,029 US7662952B2 (en) 2002-02-20 2008-09-02 RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acid (siNA)
US12/203,731 US7659390B2 (en) 2002-02-20 2008-09-03 RNA interference mediated inhibition of muscarinic colinergic receptor gene expression using short interfering nucleic acid (siNA)
US12/203,669 US7667029B2 (en) 2002-02-20 2008-09-03 RNA interference mediated inhibition of checkpoint kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US12/203,707 US7683165B2 (en) 2002-02-20 2008-09-03 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US12/204,612 US7667030B2 (en) 2002-02-20 2008-09-04 RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
US12/204,572 US7678897B2 (en) 2002-02-20 2008-09-04 RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US12/204,637 US7683166B2 (en) 2002-02-20 2008-09-04 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US12/205,558 US20090093439A1 (en) 2002-02-20 2008-09-05 RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/205,113 US7897753B2 (en) 2002-02-20 2008-09-05 RNA interference mediated inhibition of XIAP gene expression using short interfering nucleic acid (siNA)
US12/247,971 US8258288B2 (en) 2002-02-20 2008-10-08 RNA interference mediated inhibition of respiratory syncytial virus (RSV) expression using short interfering nucleic acid (siNA)
US12/253,156 US7964578B2 (en) 2001-05-18 2008-10-16 Conjugates and compositions for cellular delivery
US12/334,163 US8013143B2 (en) 2002-02-20 2008-12-12 RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA)
US12/334,197 US20090253773A1 (en) 2002-02-20 2008-12-12 RNA INTERFERENCE MEDIATED INHIBITION OF TNF AND TNF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/334,224 US20090253774A1 (en) 2002-02-20 2008-12-12 RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET DERIVED GROWTH FACTOR (PDGF) AND PLATELET DERIVED GROWTH FACTOR RECEPTOR (PDGFR) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/334,146 US20090306182A1 (en) 2002-02-20 2008-12-12 RNA INTERFERENCE MEDIATED INHIBITION OF MAP KINASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/334,181 US20090264504A1 (en) 2001-05-18 2008-12-12 RNA INTERFERENCE MEDIATED INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/418,477 US7935812B2 (en) 2002-02-20 2009-04-03 RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA)
US12/635,619 US7893248B2 (en) 2002-02-20 2009-12-10 RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA)
US12/635,228 US7858771B2 (en) 2002-02-20 2009-12-10 RNA interference mediated inhibition of muscarinic colinergic receptor gene expression using short interfering nucleic acid (siNA)
US12/640,489 US7855284B2 (en) 2002-02-20 2009-12-17 RNA interference mediated inhibition of checkpoint kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US12/640,411 US8017765B2 (en) 2000-08-30 2009-12-17 RNA interference mediated treatment of alzheimer's disease using short interfering nucleic acid (siNA)
US12/640,668 US7956178B2 (en) 2002-02-20 2009-12-17 RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acid (siNA)
US12/640,743 US8013146B2 (en) 2002-02-20 2009-12-17 RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
US12/683,349 US7910725B2 (en) 2002-02-20 2010-01-06 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US12/683,996 US7923549B2 (en) 2002-02-20 2010-01-07 RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US12/689,714 US7897755B2 (en) 2002-02-20 2010-01-19 RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US12/693,900 US7897756B2 (en) 2002-02-20 2010-01-26 RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA)
US12/693,787 US8153778B2 (en) 2002-02-20 2010-01-26 RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US12/712,985 US7897757B2 (en) 2002-02-20 2010-02-25 RNA interference mediated inhibition of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US12/717,511 US20100227911A1 (en) 2002-02-20 2010-03-04 RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/724,651 US7928220B2 (en) 2002-02-20 2010-03-16 RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA)
US12/748,075 US20100240730A1 (en) 2002-02-20 2010-03-26 RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
US12/765,450 US7977472B2 (en) 2002-02-20 2010-04-22 RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA)
US12/765,818 US20100228018A1 (en) 2002-02-20 2010-04-22 RNA INTERFERENCE MEDIATED INHIBITION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US12/777,913 US7985853B2 (en) 2002-02-20 2010-05-11 RNA interference mediated inhibition of platelet derived growth factor (PDGF) and platelet derived growth factor receptor (PDGFR) gene expression using short interfering nucleic acid (siNA)
US12/777,816 US8008473B2 (en) 2002-02-20 2010-05-11 RNA interference mediated inhibition of TNF and TNF receptor gene expression using short interfering nucleic acid (siNA)
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US11/299,391 Continuation-In-Part US7517864B2 (en) 2001-05-18 2005-12-09 RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
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US10/826,966 Continuation-In-Part US20050032733A1 (en) 2000-02-11 2004-04-16 RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
US10/840,731 Continuation-In-Part US20050137153A1 (en) 2002-02-20 2004-05-06 RNA interference mediated inhibition of alpha-1 antitrypsin (AAT) gene expression using short interfering nucleic acid (siNA)
US10/923,536 Continuation-In-Part US20070042983A1 (en) 2001-05-18 2004-08-20 RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
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