Application of RNA interference in treating human diseases

Gene silencing can occur either through repression of transcription, termed transcriptional gene silencing (TGS), or through translation repression andmRNA degradation, termed posttranscriptional gene silencing (PTGS). PTGS results from sequence-specific mRNA degradation in the cytoplasm without dramatic changes in transcription of corresponding gene in nucleus. Both TGS and PTGS are used to regulate endogenous genes. Interestingly, mechanisms for gene silencing also protect the genome from transposons and viruses. In this paper, we first review RNAi mechanism and then focus on some of its applications in biomedical research such as treatment for HIV, viral hepatitis, cardiovascular and cerebrovascular diseases, metabolic disease, neurodegenerative disorders and cancer.

[1]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[2]  F. Catteruccia,et al.  Stable and heritable gene silencing in the malaria vector Anopheles stephensi. , 2003, Nucleic acids research.

[3]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[4]  M. Mathews,et al.  Interactions between double-stranded RNA regulators and the protein kinase DAI , 1992, Molecular and cellular biology.

[5]  Aseem Kumar,et al.  Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Rosenberg,et al.  Animal Pneumoviruses: Molecular Genetics and Pathogenesis , 2004, Clinical Microbiology Reviews.

[7]  A. Borkhardt,et al.  Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi) , 2002, Oncogene.

[8]  B. Williams,et al.  RNA interference and double-stranded-RNA-activated pathways. , 2004, Biochemical Society transactions.

[9]  T. Tuschl,et al.  The Human DiGeorge Syndrome Critical Region Gene 8 and Its D. melanogaster Homolog Are Required for miRNA Biogenesis , 2004, Current Biology.

[10]  R. Bernards,et al.  Stable suppression of tumorigenicity by virus-mediated RNA interference. , 2002, Cancer cell.

[11]  D. Weissman,et al.  Small Interfering RNAs Mediate Sequence-Independent Gene Suppression and Induce Immune Activation by Signaling through Toll-Like Receptor 31 , 2004, The Journal of Immunology.

[12]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[13]  R. Hanson,et al.  Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. , 1997, Annual review of biochemistry.

[14]  Andrew Fire,et al.  The rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans , 1999, Cell.

[15]  John Rossi,et al.  Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[16]  P. Sharp,et al.  Embryonic stem cell-specific MicroRNAs. , 2003, Developmental cell.

[17]  A Rzhetsky,et al.  Molecular pathogenesis of B-cell chronic lymphocytic leukemia: analysis of 13q14 chromosomal deletions. , 2000, Current topics in microbiology and immunology.

[18]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[19]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[20]  F. Hirsch,et al.  IFN‐γ induces apoptosis in mouse embryonic stem cells, a putative mechanism of its embryotoxicity , 2000 .

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

[22]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Flavell,et al.  Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 , 2001, Nature.

[24]  R. Surabhi,et al.  RNA Interference Directed against Viral and Cellular Targets Inhibits Human Immunodeficiency Virus Type 1 Replication , 2002, Journal of Virology.

[25]  Anton P. McCaffrey,et al.  Inhibition of hepatitis B virus in mice by RNA interference , 2003, Nature Biotechnology.

[26]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[28]  Fischer L Tan,et al.  Application of RNAi to cancer research and therapy. , 2005, Frontiers in bioscience : a journal and virtual library.

[29]  M. Yoder,et al.  Application of RNA interference to study stem cell function: current status and future perspectives , 2005, Biology of the cell.

[30]  S. Angaji,et al.  Application of RNA interference in plants. , 2010 .

[31]  Xiaofeng Cao,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003, Science.

[32]  Peter A. Jones,et al.  Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. , 2006, Cancer cell.

[33]  C. Taniguchi,et al.  Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. , 2005, The Journal of clinical investigation.

[34]  D. Weissman,et al.  Inhibition of HIV-1 Infection by Small Interfering RNA-Mediated RNA Interference1 , 2002, The Journal of Immunology.

[35]  Sharad Kumar,et al.  Debcl, a Proapoptotic Bcl-2 Homologue, Is a Component of the Drosophila melanogaster Cell Death Machinery , 2000, The Journal of cell biology.

[36]  S. Tutton,et al.  , Eric Pierce and Kyonggeun Cells in Undifferentiated Mouse Embryonic Stem Specific Double-Stranded RNA Interference , 2001 .

[37]  Mario Stevenson,et al.  Therapeutic potential of RNA interference. , 2004, The New England journal of medicine.

[38]  R. Lehmann,et al.  A Noncoding RNA Is Required for the Repression of RNApolII-Dependent Transcription in Primordial Germ Cells , 2004, Current Biology.

[39]  C. Rice,et al.  Efficient initiation of HCV RNA replication in cell culture. , 2000, Science.

[40]  Henning Urlaub,et al.  Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi , 2002, Cell.

[41]  C. Napoli,et al.  Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. , 1990, The Plant cell.

[42]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

[43]  H. Vaucheret,et al.  Post-transcriptional gene silencing in plants. , 2001, Journal of cell science.

[44]  J. Vinten-johansen,et al.  Myocardial apoptosis and ischemic preconditioning. , 2002, Cardiovascular research.

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

[46]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[47]  J. Silver,et al.  Replication of Subgenomic Hepatitis C Virus Rnas in a Hepatoma Cell Line , 1999 .

[48]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[49]  Michael T. McManus,et al.  MicroRNAs and cancer. , 2003, Seminars in cancer biology.

[50]  R. Berro,et al.  RNA interference directed to CDK2 inhibits HIV-1 transcription. , 2005, Virology.

[51]  Mark P. Mattson,et al.  Apoptosis in neurodegenerative disorders , 2000, Nature Reviews Molecular Cell Biology.

[52]  S. Lemon,et al.  Selectable Subgenomic and Genome-Length Dicistronic RNAs Derived from an Infectious Molecular Clone of the HCV-N Strain of Hepatitis C Virus Replicate Efficiently in Cultured Huh7 Cells , 2002, Journal of Virology.

[53]  Guiliang Tang,et al.  siRNA and miRNA: an insight into RISCs. , 2005, Trends in biochemical sciences.

[54]  J. M. Velkey,et al.  Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells , 2003, Genesis.

[55]  Yang Shi,et al.  Mammalian RNAi for the masses. , 2003, Trends in genetics : TIG.

[56]  M. Carmell,et al.  Posttranscriptional Gene Silencing in Plants , 2006 .

[57]  De-Pei Liu,et al.  The role of small RNAs in human diseases: Potential troublemaker and therapeutic tools , 2005, Medicinal research reviews.

[58]  U. Kutay,et al.  Nuclear Export of MicroRNA Precursors , 2004, Science.

[59]  Ravi Jain,et al.  MicroRNA-143 Regulates Adipocyte Differentiation* , 2004, Journal of Biological Chemistry.

[60]  J. Rowley,et al.  Duplexes of 21‐nucleotide RNAs mediate RNA interference in differentiated mouse ES cells , 2003, Biology of the cell.

[61]  Anastasia Khvorova,et al.  Induction of the interferon response by siRNA is cell type- and duplex length-dependent. , 2006, RNA.

[62]  H. Lage,et al.  Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi) , 2003, FEBS letters.

[63]  P. Zamore.  RNA Interference: Big Applause for Silencing in Stockholm , 2006, Cell.

[64]  J. Hardy,et al.  The genetic causes of neurodegenerative diseases. , 2001, Journal of Alzheimer's disease : JAD.

[65]  Olivier Voinnet,et al.  Two classes of short interfering RNA in RNA silencing , 2002, The EMBO journal.

[66]  D. Baulcombe.  Unwinding RNA Silencing , 2000, Science.

[67]  Ali Ehsani,et al.  Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells , 2002, Nature Biotechnology.

[68]  D. Rubinsztein.  Lessons from animal models of Huntington's disease. , 2002, Trends in genetics : TIG.

[69]  Nektarios Tavernarakis,et al.  Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes , 2000, Nature Genetics.

[70]  M. Matzke,et al.  RNA-based silencing strategies in plants. , 2001, Current opinion in genetics & development.

[71]  S. Barik,et al.  Inhibition of respiratory viruses by nasally administered siRNA , 2005, Nature Medicine.

[72]  M. Stevenson,et al.  Modulation of HIV-1 replication by RNA interference , 2002, Nature.

[73]  B. Ramratnam,et al.  Human Immunodeficiency Virus Type 1 Escape from RNA Interference , 2003, Journal of Virology.

[74]  Kazunari Taira,et al.  A Small Modulatory dsRNA Specifies the Fate of Adult Neural Stem Cells , 2004, Cell.

[75]  Stephan Wolf,et al.  Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma , 1998, Oncogene.

[76]  V. Wacheck,et al.  Short interfering RNA (siRNA): tool or therapeutic? , 2006, Clinical science.

[77]  W. Tatton,et al.  Apoptosis in neurodegenerative disorders: potential for therapy by modifying gene transcription. , 1997, Journal of neural transmission. Supplementum.

[78]  Robert H. Silverman,et al.  Activation of the interferon system by short-interfering RNAs , 2003, Nature Cell Biology.

[79]  J. Irelan,et al.  Transgene silencing of the al‐1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA‐DNA interactions or DNA methylation. , 1996, The EMBO journal.

[80]  T. Tuschl,et al.  Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate , 2001, The EMBO journal.

[81]  J. Mol,et al.  Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. , 1990, The Plant cell.

[82]  T. Burdon,et al.  Oct‐4 Knockdown Induces Similar Patterns of Endoderm and Trophoblast Differentiation Markers in Human and Mouse Embryonic Stem Cells , 2004, Stem cells.

[83]  S. Barik,et al.  New drugs and treatment for respiratory syncytial virus , 2004, Reviews in medical virology.

[84]  P. Campochiaro.  Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders , 2006, Gene Therapy.

[85]  J. Rossi,et al.  Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[86]  Sangdun Choi,et al.  Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy , 2005, Nature Biotechnology.

[87]  K. Reddy,et al.  India wakes up to the threat of cardiovascular diseases. , 2007, Journal of the American College of Cardiology.

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

[89]  Wei Ge,et al.  Synthetic shRNAs as potent RNAi triggers , 2005, Nature Biotechnology.

[90]  J. M. Velkey,et al.  Oct 4 RNA Interference Induces Trophectoderm Differentiation in Mouse Embryonic Stem Cells † , 2003 .

[91]  A. Ganser,et al.  Specific inhibition of bcr-abl gene expression by small interfering RNA. , 2003, Blood.

[92]  R. Scheule,et al.  Development of catheter-based procedures for transducing the isolated rabbit liver with plasmid DNA. , 2002, Human gene therapy.

[93]  Y. Wan,et al.  RNA-mediated gene regulation system: now and the future (Review). , 2002, International journal of molecular medicine.

[94]  J. Ray,et al.  Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants , 1990, Molecular and General Genetics MGG.

[95]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[96]  B. Clotet,et al.  Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication , 2002, AIDS.

[97]  Molecular Biology Select , 2009, Cell.

[98]  R. Plasterk,et al.  Dicers at RISC The Mechanism of RNAi , 2004, Cell.

[99]  B. Williams,et al.  PKR; a sentinel kinase for cellular stress , 1999, Oncogene.

[100]  B. Cullen,et al.  Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference , 2002, Journal of Virology.

[101]  R. Bartenschlager,et al.  Characterization of Cell Lines Carrying Self-Replicating Hepatitis C Virus RNAs , 2001, Journal of Virology.

[102]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[103]  J. Weiler,et al.  Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? , 2006, Gene Therapy.

[104]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[105]  G. Macino,et al.  Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences , 1992, Molecular microbiology.

[106]  J. Church,et al.  siRNA-DIRECTED INHIBITION OF HIV-1 INFECTION , 2003, Pediatrics.

[107]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[108]  N. Miyano-Kurosaki,et al.  Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference. , 2002, Nucleic acids research.

[109]  G. Hannon,et al.  Unlocking the potential of the human genome with RNA interference , 2004, Nature.

[110]  M. Manns,et al.  Caspase 8 small interfering RNA prevents acute liver failure in mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[111]  B. Cullen,et al.  Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. , 2004, RNA.

[112]  H. Vornlocher,et al.  Inhibition of bcr-abl gene expression by small interfering RNA sensitizes for imatinib mesylate (STI571). , 2003, Blood.

[113]  F. Kafatos,et al.  The complex interplay between mosquito positive and negative regulators of Plasmodium development. , 2005, Current opinion in microbiology.

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

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