siRNA as a new drug: intellectual property

RNA interference (RNAi) is a powerful tool for gene function analysis and drug discovery research. In this process, small interfering RNA (siRNA) silences the expression of a specific protein, which is encoded by a nucleic acid sequence that is complementary to the sequence of the siRNA. The reproducibility, specificity and magnitude of the silencing effect have stimulated a fast adoption of this process as the method of choice to study loss-of-function phenotypes and validate drug targets. In addition, siRNA may offer promise as a new drug. For successful application as a therapeutic, stability in the biological environment and efficiency of target cell entry of siRNA need to be addressed. This review describes scientific literature and patents (applications) related to the use of RNAi and innovations on siRNA stability and invivo delivery to target cells.

[1]  J. Behr,et al.  Lipid‐mediated siRNA delivery down‐regulates exogenous gene expression in the mouse brain at picomolar levels , 2005, The journal of gene medicine.

[2]  Raymond M Schiffelers,et al.  Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes: therapeutic strategy for herpetic stromal keratitis. , 2004, The American journal of pathology.

[3]  R. Tomanin,et al.  Why do we need new gene therapy viral vectors? Characteristics, limitations and future perspectives of viral vector transduction. , 2004, Current gene therapy.

[4]  Matthias John,et al.  Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs , 2004, Nature.

[5]  M. Stevenson.  Therapeutic potential of RNA interference , 2004, The New England journal of medicine.

[6]  S. Chae,et al.  Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. , 2004, The Journal of clinical investigation.

[7]  J. Lieberman,et al.  Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Pulido,et al.  RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis. , 2004, Molecular vision.

[9]  Matthias John,et al.  Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. , 2004, Bioorganic & medicinal chemistry letters.

[10]  N. K. Verma,et al.  RNA‐mediated gene silencing: mechanisms and its therapeutic applications , 2004, Journal of clinical pharmacy and therapeutics.

[11]  K. Taira,et al.  Induction of DNA methylation and gene silencing by short interfering RNAs in human cells , 2004, Nature.

[12]  C. Newgard,et al.  An adenovirus vector for efficient RNA interference-mediated suppression of target genes in insulinoma cells and pancreatic islets of langerhans. , 2004, Diabetes.

[13]  K. Morris,et al.  Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells , 2004, Science.

[14]  J. Wengel,et al.  Locked nucleic acid: a potent nucleic acid analog in therapeutics and biotechnology. , 2004, Oligonucleotides.

[15]  D. Lewis,et al.  A facile nonviral method for delivering genes and siRNAs to skeletal muscle of mammalian limbs. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[16]  S. Ashley,et al.  Retrovirally mediated RNA interference targeting the M2 subunit of ribonucleotide reductase: A novel therapeutic strategy in pancreatic cancer. , 2004, Surgery.

[17]  N. Caplen,et al.  Gene Therapy Progress and Prospects. Downregulating gene expression: the impact of RNA interference , 2004, Gene Therapy.

[18]  H. Paulson,et al.  RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia , 2004, Nature Medicine.

[19]  J. Contreras,et al.  Caspase-8 and caspase-3 small interfering RNA decreases ischemia/reperfusion injury to the liver in mice. , 2004 .

[20]  J. Rossi,et al.  Recent applications of RNAi in mammalian systems. , 2004, Current pharmaceutical biotechnology.

[21]  J. Contreras,et al.  Caspase-8 and caspase-3 small interfering RNA decreases ischemia/reperfusion injury to the liver in mice. , 2004, Surgery.

[22]  T. Tuschl,et al.  Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. , 2004, Molecular cell.

[23]  Lonnie D Shea,et al.  Controlled release systems for DNA delivery. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[24]  Fran Lewitter,et al.  siRNA Selection Server: an automated siRNA oligonucleotide prediction server , 2004, Nucleic Acids Res..

[25]  René H Medema,et al.  Optimizing RNA interference for application in mammalian cells. , 2004, The Biochemical journal.

[26]  Qing Ge,et al.  Inhibition of influenza virus production in virus-infected mice by RNA interference. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Julian Downward,et al.  Science, medicine, and the future: RNA interference , 2004 .

[28]  Anton P. McCaffrey,et al.  In vivo activity of nuclease-resistant siRNAs. , 2004, RNA.

[29]  M. Amarzguioui,et al.  An algorithm for selection of functional siRNA sequences. , 2004, Biochemical and biophysical research communications.

[30]  C. Wahlestedt,et al.  Functional comparison of single- and double-stranded siRNAs in mammalian cells. , 2004, Biochemical and biophysical research communications.

[31]  M. Duxbury,et al.  RNA interference: a practical approach. , 2004, The Journal of surgical research.

[32]  Thomas Tuschl,et al.  siRNAs: applications in functional genomics and potential as therapeutics , 2004, Nature Reviews Drug Discovery.

[33]  K. Morris,et al.  Anti-HIV-1 gene expressing lentiviral vectors as an adjunctive therapy for HIV-1 infection. , 2004, Current HIV research.

[34]  Z. Paroo,et al.  Biodistribution of phosphodiester and phosphorothioate siRNA. , 2004, Bioorganic & medicinal chemistry letters.

[35]  N. Ballew.  Benitec, Ltd. Gene silencing from down under. , 2004, Chemistry & biology.

[36]  B. Cullen,et al.  Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages by Using Tat- or CCR5-Specific Small Interfering RNAs Expressed from a Lentivirus Vector , 2003, Journal of Virology.

[37]  H. Giladi,et al.  Small interfering RNA inhibits hepatitis B virus replication in mice. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[38]  T. Rana,et al.  siRNA function in RNAi: a chemical modification analysis. , 2003, RNA.

[39]  P. Chaudhary,et al.  Use of adeno-associated viral vector for delivery of small interfering RNA , 2003, Oncogene.

[40]  Claes Wahlestedt,et al.  Effective small interfering RNAs and phosphorothioate antisense DNAs have different preferences for target sites in the luciferase mRNAs. , 2003, Biochemical and biophysical research communications.

[41]  A. Klippel,et al.  Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. , 2003, Nucleic acids research.

[42]  M. Morris,et al.  Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells. , 2003, Nucleic acids research.

[43]  Susanna Wu-Pong,et al.  Innovations in oligonucleotide drug delivery , 2003, Journal of Pharmaceutical Sciences.

[44]  M. Amarzguioui,et al.  Similar behaviour of single-strand and double-strand siRNAs suggests they act through a common RNAi pathway. , 2003, Nucleic acids research.

[45]  Mouldy Sioud,et al.  Gene silencing by systemic delivery of synthetic siRNAs in adult mice. , 2003, Journal of molecular biology.

[46]  Thomas Tuschl,et al.  Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. , 2003, Antisense & nucleic acid drug development.

[47]  M. Dobbelstein.  Viruses in therapy--royal road or dead end? , 2003, Virus research.

[48]  R. Schultz,et al.  Transgenic RNAi in mouse oocytes: a simple and fast approach to study gene function. , 2003, Developmental biology.

[49]  Jens Kurreck,et al.  Antisense technologies. Improvement through novel chemical modifications. , 2003, European journal of biochemistry.

[50]  Judy Lieberman,et al.  RNA interference targeting Fas protects mice from fulminant hepatitis , 2003, Nature Medicine.

[51]  M. Amarzguioui,et al.  Tolerance for mutations and chemical modifications in a siRNA. , 2003, Nucleic acids research.

[52]  K. Kiyosawa,et al.  RNA interference may be more potent than antisense RNA in human cancer cell lines , 2003, Clinical and experimental pharmacology & physiology.

[53]  K. Taira,et al.  Effects on RNA interference in gene expression (RNAi) in cultured mammalian cells of mismatches and the introduction of chemical modifications at the 3'-ends of siRNAs. , 2002, Antisense & nucleic acid drug development.

[54]  Haibin Xia,et al.  siRNA-mediated gene silencing in vitro and in vivo , 2002, Nature Biotechnology.

[55]  Deborah R. Wilson.  Viral-mediated gene transfer for cancer treatment. , 2002, Current pharmaceutical biotechnology.

[56]  J. Birchler,et al.  RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. , 2002, Molecular cell.

[57]  Titia Sijen,et al.  On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing , 2001, Cell.

[58]  K. Nishikura,et al.  A Short Primer on RNAi RNA-Directed RNA Polymerase Acts as a Key Catalyst , 2001, Cell.

[59]  R. Gambari.  Peptide-nucleic acids (PNAs): a tool for the development of gene expression modifiers. , 2001, Current pharmaceutical design.

[60]  A. Caudy,et al.  Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi , 2001, Science.

[61]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[62]  P. Couvreur,et al.  Nanoparticulate systems for the delivery of antisense oligonucleotides. , 2001, Advanced drug delivery reviews.

[63]  Amy A. Caudy,et al.  Post-transcriptional gene silencing by double-stranded RNA , 2001, Nature Reviews Genetics.

[64]  A. Caudy,et al.  Role for a bidentate ribonuclease in the initiation step of RNA interference , 2001 .

[65]  T. Tuschl,et al.  RNA interference is mediated by 21- and 22-nucleotide RNAs. , 2001, Genes & development.

[66]  B. Sikic,et al.  Clinical studies of antisense therapy in cancer. , 2000, Frontiers in bioscience : a journal and virtual library.

[67]  Phillip D. Zamore,et al.  RNA Interference , 2000, Science.

[68]  S. Hammond,et al.  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells , 2000, Nature.

[69]  Magdalena Zernicka-Goetz,et al.  Specific interference with gene function by double-stranded RNA in early mouse development , 2000, Nature Cell Biology.

[70]  M. Kirby,et al.  Double-stranded RNA injection produces null phenotypes in zebrafish. , 2000, Developmental biology.

[71]  A. Wargelius,et al.  Double-stranded RNA induces specific developmental defects in zebrafish embryos. , 1999, Biochemical and biophysical research communications.

[72]  A. Fire,et al.  RNA-triggered gene silencing. , 1999, Trends in genetics : TIG.

[73]  A. Fire,et al.  RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Madhur Kumar,et al.  Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes , 1998, Microbiology and Molecular Biology Reviews.

[75]  A. Fire,et al.  Specific interference by ingested dsRNA , 1998, Nature.

[76]  A. Fire,et al.  Double-stranded RNA as a mediator in sequence-specific genetic silencing and co-suppression. , 1998, Trends in genetics : TIG.

[77]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[78]  J. Langland,et al.  When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. , 1996, Virology.

[79]  J. Méry,et al.  The retro-inverso form of a homeobox-derived short peptide is rapidly internalised by cultured neurones: a new basis for an efficient intracellular delivery system. , 1995, Biochemical and biophysical research communications.

[80]  P. Hwu.  Gene therapy: progress and prospects. , 1994, Contemporary urology.

[81]  J. Walker,et al.  Antisense Therapeutics , 2005, Methods in Molecular Medicine™.

[82]  R. Schiffelers,et al.  Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. , 2004, Nucleic acids research.

[83]  M. Montgomery.  RNA interference: historical overview and significance. , 2004, Methods in molecular biology.

[84]  Raymond M. Schiffelers,et al.  Pharmaceutical Prospects for RNA Interference , 2004, Pharmaceutical Research.

[85]  Stanley T Crooke,et al.  Antisense strategies. , 2004, Current molecular medicine.

[86]  N. Kosaka,et al.  Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. , 2004, Nucleic acids research.

[87]  Anton Buzdin,et al.  Improving specificity of DNA hybridization-based methods. , 2004, Nucleic acids research.

[88]  W. Walther,et al.  Viral vectors for gene transfer: a review of their use in the treatment of human diseases. , 2000, Drugs.