RNA Interference

Contents

Introduction

Effector RNA molecules

RNAi pathways are guided by small RNAs that include

SiRNA:

miRNA:

shRNA:

shRNA uses a vector introduced into cells and utilizes the U6 promoter to ensure that the shRNA is always expressed. This vector is usually passed on to daughter cells, allowing the gene silencing to be inherited. The shRNA hairpin structure is cleaved by the cellular machinery into siRNA, which is then bound to the RNA-induced silencing complex (RISC). This complex binds to and cleaves mRNAs which match the siRNA that is bound to it. Source

Others:

Cellular Mechanism

Mechanism of RNA interference in mammalian cells

siRNA Delivery

Challenges of in vivo siRNA delivery

Other mechanisms of siRNA delivery include:

Applications

Applications of in vivo siRNA delivery in disease models

? RNAi technology is proving to be useful to analyze quickly the functions of a number of genes in a wide variety of organisms.

? RNAi technology has been successfully applied to identify genes with essential roles in biochemical signaling cascades, embryonic development, and other basic cellular process.

? In plants, gene knockdown-related functional studies are being carried out efficiently when transgenes are present in the form of hairpin (or RNAi) constructs. Plant endotoxins could also be removed if the toxin biosynthesis genes are targeted with the RNAi constructs, like theobromine synthase of the coffee plant was knocked down with the hairpin construct of the transgene, leading to the production of decaffeinated coffee plants.

? RNAi may facilitate drug screening and development by identifying genes that can confer drug resistance or genes whose mutant phenotypes are ameliorated by drug treatment, providing information about the modes of action of novel compounds.

? It may also be a method of choice to study the simultaneous functions of a number of analogous genes in organisms in which redundancy exists with respect to a particular function, because many of these genes can be silenced simultaneously.

? siRNAs have been shown to inhibit infection by human immunodeficiency virus, poliovirus, and hepatitis C virus in cultured cell lines. siRNAs can successfully be used to silence genes expressed in respiratory syncytial virus, an RNA virus that causes severe respiratory disease in neonates and infants. siRNA treatment has also been shown to reduce the expression of the BCR-ABL oncoprotein in leukemia and lymphoma cell lines, leading to apoptosis in these cells. With respect to future medical applications, siRNA-based therapy seems to have a great potential to combat carcinomas, myeloma, and cancer caused by overexpression of an oncoprotein or generation of an oncoprotein by chromosomal translocation and point mutations. Source

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Intellectual Property

Search Strategy

Micropat

Years: 1836 to 2008

S.No Concept Scope Query # of hits
1 siRNA Claims, Title or Abstract (siRNA*1 OR (short ADJ1 interfering ADJ1 RNA*1) OR (short ADJ1 interfering ADJ1 nucleic ADJ1 acid*1) OR (short ADJ1 interfering ADJ1 NA*1) OR siNA OR siNAs OR (si ADJ1 RNA*1)) 7203
2 RNAi Claims, Title or Abstract (RNA*1 NEAR2 interfer*) OR RNAi* 9057
3     1 OR 2 13541
4 Delivery Claims, Title or Abstract (Deliver* OR Formulation*1 OR conjugat*1 OR administ*) 1418602
5     3 AND 4 5964
6     Unique records 3592


Non-Patents

Scirus and PubMed

S.No Query # of hits
1 (((siRNA OR (short interfering RNA) OR (short interfering nucleic acid) OR siNA OR siNAs) OR (RNA interfer) OR RNAi OR (Interfering RNA)) AND (Deliver OR Delivery OR Formulation OR conjugat OR administ)) ~2000 articles (399 reviews)


Note: The search strategy can be modified in accordance to the Clients' requirements.

It can be narrowed down at concepts like

Analysis Taxonomy

siRNA Taxonomy

Analysis

Patent Literature

S.No Patent / Publication Number Date of Publication Application Date Assignee / Applicant Title Dolcera Summary
1 EP1946761 7/23/2008 10/17/2006 Otsuka Pharmaceutical Co., Ltd. CARRIER COMPOSITION FOR NUCLEIC ACID TRANSPORT A nucleic acid like siRNA carrier composition comprising of cationic lipids is used in the siRNA delivery to the target cells with low toxicity and high safety.
2 US7345027 3/18/2008 6/8/2006 The Trustees of the University of Pennsylvania Compositions and methods for siRNA inhibition of angiogenesis A method of inhibiting angiogenesis and its related disorders using RNA interference, where siRNA alone or in combination with a pharmaceutical agent delivered using liposomes, specific to vascular endothelial growth factor (VEGF) gene and the VEGF receptor genes Flt-1 and Flk-1/KDR, inhibit expression of these genes.
3 US20040242518 12/2/2004 9/29/2003 Massachusetts Institute of Technology Influenza therapeutic A method of inhibiting influenza infection or replication using RNAi technology, where siRNA is targeted to the infected cells containing the viral RNA using a delivery agent like polymers, peptides, liposomes, etc.
4 US20070003519 1/4/2007 10/20/2006 None Targets for tumor growth inhibition A method of treating cancer using RNAi technology, where siRNA interferes with target ICT1031, ICT1024, ICT 1025, or ICT1003 gene expression and causes post-transcriptional silencing, where siRNA is delivered in the naked or vector form.
5 US20080020058 1/24/2008 10/24/2006 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules A method of treating diseases associated with gene expression using siRNA along with delivery agents like nano-particles.
6 WO2006086772 8/17/2006 2/10/2006 GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES METHOD OF DIAGNOSING AND TREATING CANCER USING B-CATENIN SPLICE VARIANTS A method and composition for treating f3-catenin gene (CTNNB 1) related diseases like cancer, using RNAi construct like siRNA, delivered using liposomes. The siRNA attenuates expression of a gene resulting in reducing proliferation.
7 WO2008054544 5/8/2008 5/22/2007 THE CBR INSTITUTE FOR BIOMEDICAL RESEARCH, INC | NARASIMHASWAMY, Manjunath | SHANKAR, Premlata | KUMAR, Priti METHOD FOR DELIVERY ACROSS THE BLOOD BRAIN BARRIER A composition and method of delivering therapeutic agents like siRNA, shRNAs across the blood-brain barrier to the target cells or tissues for the treatment of neurologically related disorders.
8 WO2008039254 4/3/2008 5/31/2007 GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | YINGLING, Yaroslava, G. | SHAPIRO, Bruce, A. RNA NANOPARTICLES AND NANOTUBES A method of providing polyvalent RNA nanoparticles with RNA motifs as building blocks to form RNA nanotubes which are further suitable for therapeutic or diagnostic use in a number of diseases or disorders.

RNAi Database

Spread sheet of Sample patents(8) analysis

Spread sheet of Clinical Trials on siRNA delivery

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Email: info@dolcera.com
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