Improving the efficiency of RNA interference in mammals

RNA interference (RNAi) has been very successfully applied as a gene-silencing technology in both plants and invertebrates, but many practical obstacles need to be overcome before it becomes viable in mammalian systems. Greater specificity and efficiency of RNAi in mammals is being achieved by improving the design and selection of small interfering RNAs (siRNAs), by increasing the efficacy of their delivery to cells and organisms, and by engineering their conditional expression. Genome-wide functional RNAi screens, which are predominantly done in worms and flies, have now begun to revolutionize large-scale loss-of-function studies in mammals.

[1]  P. Sharp,et al.  RNAi and double-strand RNA. , 1999, Genes & development.

[2]  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.

[3]  Michael T. McManus,et al.  Gene silencing in mammals by small interfering RNAs , 2002, Nature Reviews Genetics.

[4]  Anne E Carpenter,et al.  Systematic genome-wide screens of gene function , 2004, Nature Reviews Genetics.

[5]  F. Leenders,et al.  Inducible shRNA expression for application in a prostate cancer mouse model. , 2003, Nucleic acids research.

[6]  Patrick J. Paddison,et al.  An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo , 2003, Nature Genetics.

[7]  A. Gewirtz,et al.  Nucleic-acid therapeutics: basic principles and recent applications , 2002, Nature Reviews Drug Discovery.

[8]  A. Ganser,et al.  Modulation of Gene Expression by Lentiviral-Mediated Delivery of Small Interfering RNA , 2003, Cell cycle.

[9]  Phillip A Sharp,et al.  siRNAs can function as miRNAs , 2003 .

[10]  D. Baltimore,et al.  Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Sabatini,et al.  Microarrays of cells expressing defined cDNAs , 2001, Nature.

[12]  S. Ohashi,et al.  Sequence‐specific gene silencing in murine muscle induced by electroporation‐mediated transfer of short interfering RNA , 2004, The journal of gene medicine.

[13]  B. Nuttin,et al.  Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. , 2003, Human gene therapy.

[14]  M. Wiznerowicz,et al.  Conditional Suppression of Cellular Genes: Lentivirus Vector-Mediated Drug-Inducible RNA Interference , 2003, Journal of Virology.

[15]  G. Hannon RNA interference : RNA , 2002 .

[16]  H. Paulson,et al.  Toward therapy for DYT1 dystonia: Allele‐specific silencing of mutant TorsinA , 2003, Annals of neurology.

[17]  B. Li,et al.  Expression profiling reveals off-target gene regulation by RNAi , 2003, Nature Biotechnology.

[18]  Michael T. McManus,et al.  A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference , 2003, Nature Genetics.

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

[20]  Inder M Verma,et al.  A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Gary Ruvkun,et al.  Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes , 2003, Nature.

[22]  R. Carthew,et al.  Heritable gene silencing in Drosophila using double-stranded RNA , 2000, Nature Biotechnology.

[23]  M. Okabe,et al.  Small interfering RNA and gene silencing in transgenic mice and rats , 2002, FEBS letters.

[24]  Peter G Schultz,et al.  An approach to genomewide screens of expressed small interfering RNAs in mammalian cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[25]  M. Amarzguioui,et al.  Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor. , 2002, Nucleic acids research.

[26]  Ronald W. Davis,et al.  Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar–coding strategy , 1996, Nature Genetics.

[27]  K. Taira,et al.  Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells. , 2003, Nucleic acids research.

[28]  René Bernards,et al.  Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB , 2003, Nature.

[29]  T. Tuschl,et al.  Analysis of gene function in somatic mammalian cells using small interfering RNAs. , 2002, Methods.

[30]  A. Coulson,et al.  A functional genomic analysis of cell morphology using RNA interference , 2003, Journal of biology.

[31]  A. Reynolds,et al.  Rational siRNA design for RNA interference , 2004, Nature Biotechnology.

[32]  E. Dougherty,et al.  RNAi microarray analysis in cultured mammalian cells. , 2003, Genome research.

[33]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[34]  G. Stamatoyannopoulos,et al.  Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. , 2003, Cancer research.

[35]  T. Rana,et al.  RNAi in human cells: basic structural and functional features of small interfering RNA. , 2002, Molecular cell.

[36]  F. Chisari,et al.  Interference of hepatitis C virus RNA replication by short interfering RNAs , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  P. Zamore,et al.  ATP Requirements and Small Interfering RNA Structure in the RNA Interference Pathway , 2001, Cell.

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

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

[40]  M. Wigler,et al.  Design of a retroviral-mediated ecdysone-inducible system and its application to the expression profiling of the PTEN tumor suppressor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[41]  K Weber,et al.  Identification of essential genes in cultured mammalian cells using small interfering RNAs. , 2001, Journal of cell science.

[42]  G. Hannon,et al.  Inducible, reversible, and stable RNA interference in mammalian cells , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  C. Lawrence,et al.  A statistical sampling algorithm for RNA secondary structure prediction. , 2003, Nucleic acids research.

[44]  T. Pawson,et al.  Transgenic RNA interference in ES cell–derived embryos recapitulates a genetic null phenotype , 2003, Nature Biotechnology.

[45]  John J Rossi,et al.  Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase , 2004, Nature Biotechnology.

[46]  S. Ishii,et al.  Generation of Ski-knockdown mice by expressing a long double-strand RNA from an RNA polymerase II promoter. , 2003, Genes & development.

[47]  Haibin Xia,et al.  Allele-specific silencing of dominant disease genes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[49]  J. Leysen,et al.  Evaluation of the tetracycline‐ and ecdysone‐inducible systems for expression of neurotransmitter receptors in mammalian cells , 2001, The European journal of neuroscience.

[50]  Lawrence Lum,et al.  Identification of Hedgehog Pathway Components by RNAi in Drosophila Cultured Cells , 2003, Science.

[51]  F. Holstege,et al.  Specific inhibition of gene expression using a stably integrated, inducible small‐interfering‐RNA vector , 2003, EMBO reports.

[52]  De-Pei Liu,et al.  Retrovirus vector-mediated stable gene silencing in human cell. , 2004, Biochemical and biophysical research communications.

[53]  Georg Sczakiel,et al.  The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. , 2003, Nucleic acids research.

[54]  Serge Batalov,et al.  Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. , 2003, Molecular cell.

[55]  D. Dykxhoorn,et al.  Killing the messenger: short RNAs that silence gene expression , 2003, Nature Reviews Molecular Cell Biology.

[56]  N. Perrimon,et al.  Genome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells , 2004, Science.

[57]  W. Huttner,et al.  Tissue-specific RNA interference in postimplantation mouse embryos with endoribonuclease-prepared short interfering RNA , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[58]  K. Ui-Tei,et al.  Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. , 2004, Nucleic acids research.

[59]  Robert M Sears,et al.  Local gene knockdown in the brain using viral-mediated RNA interference , 2003, Nature Medicine.

[60]  Andrew G Fraser,et al.  Genome-Wide RNAi of C. elegans Using the Hypersensitive rrf-3 Strain Reveals Novel Gene Functions , 2003, PLoS biology.

[61]  P. Zipperlen,et al.  Functional genomic analysis of C. elegans chromosome I by systematic RNA interference , 2000, Nature.

[62]  C. F. Bennett,et al.  Efficient Reduction of Target RNAs by Small Interfering RNA and RNase H-dependent Antisense Agents , 2003, The Journal of Biological Chemistry.

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

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

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

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

[67]  S. Hammond,et al.  RNA interference: a promising approach to antiviral therapy? , 2002, Trends in molecular medicine.

[68]  G. Hannon,et al.  Germline transmission of RNAi in mice , 2003, Nature Structural Biology.

[69]  R. Wagner,et al.  A chemical modification method for the structural analysis of RNA and RNA-protein complexes within living cells. , 1998, Analytical biochemistry.

[70]  N. Déglon,et al.  Lentiviral-mediated RNA interference. , 2002, Human gene therapy.

[71]  E. Southern,et al.  The Efficacy of Small Interfering RNAs Targeted to the Type 1 Insulin-like Growth Factor Receptor (IGF1R) Is Influenced by Secondary Structure in the IGF1R Transcript* , 2003, The Journal of Biological Chemistry.

[72]  R. Iggo,et al.  Induction of an interferon response by RNAi vectors in mammalian cells , 2003, Nature Genetics.

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

[74]  A. Fire,et al.  Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[75]  R. Lehmann,et al.  Targeted mRNA degradation by double-stranded RNA in vitro. , 1999, Genes & development.

[76]  Gregory J. Hannon,et al.  Insight Review Articles , 2022 .

[77]  Cameron S. Osborne,et al.  LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1 , 2003, Science.

[78]  R. Bernards,et al.  A System for Stable Expression of Short Interfering RNAs in Mammalian Cells , 2002, Science.

[79]  M. Capecchi The new mouse genetics: altering the genome by gene targeting. , 1989, Trends in genetics : TIG.

[80]  S. Fesik,et al.  Specificity of short interfering RNA determined through gene expression signatures , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[81]  William C Hahn,et al.  Lentivirus-delivered stable gene silencing by RNAi in primary cells. , 2003, RNA.

[82]  Tyra G. Wolfsberg,et al.  Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells , 2004, Proceedings of the National Academy of Sciences of the United States of America.

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

[84]  Gary Ruvkun,et al.  A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity , 2003, Nature Genetics.

[85]  Patrick J. Paddison,et al.  RNA interference: the new somatic cell genetics? , 2002, Cancer cell.

[86]  S. Limmer,et al.  Secondary structure dimorphism and interconversion between hairpin and duplex form of oligoribonucleotides. , 1998, Antisense & nucleic acid drug development.

[87]  K. Taira,et al.  U6 promoter–driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells , 2002, Nature Biotechnology.

[88]  Bin Liu,et al.  Functional genetic analysis of mouse chromosome 11 , 2003, Nature.

[89]  Helen M Blau,et al.  Restriction enzyme–generated siRNA (REGS) vectors and libraries , 2004, Nature Genetics.

[90]  Joshua T. Jones,et al.  Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing , 2003, Nature Biotechnology.

[91]  M. Iino,et al.  Enzymatic production of RNAi libraries from cDNAs , 2004, Nature Genetics.

[92]  Reuven Agami,et al.  A large-scale RNAi screen in human cells identifies new components of the p53 pathway , 2004, Nature.

[93]  Howard Y. Chang,et al.  Genomewide view of gene silencing by small interfering RNAs , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  S. Reske,et al.  Gene silencing by adenovirus‐delivered siRNA , 2003, FEBS letters.

[95]  Vivek Mittal,et al.  High-throughput selection of effective RNAi probes for gene silencing. , 2003, Genome research.

[96]  Anastasia Khvorova,et al.  Functional siRNAs and miRNAs Exhibit Strand Bias , 2003, Cell.

[97]  B. Cullen,et al.  MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[98]  Michael T. McManus,et al.  Small Interfering RNA-Mediated Gene Silencing in T Lymphocytes1 , 2002, The Journal of Immunology.

[99]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

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

[101]  T. Giordano,et al.  RNAi: gene-silencing in therapeutic intervention. , 2002, Drug discovery today.

[102]  T. Du,et al.  Asymmetry in the Assembly of the RNAi Enzyme Complex , 2003, Cell.

[103]  R. Evans,et al.  Ecdysone-inducible gene expression in mammalian cells and transgenic mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Phillip D Zamore,et al.  Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. , 2002, Molecular cell.

[105]  W. Forrester,et al.  A DNA vector-based RNAi technology to suppress gene expression in mammalian cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[106]  René Bernards,et al.  New tools for functional mammalian cancer genetics , 2003, Nature Reviews Cancer.

[107]  S. DeRuiter,et al.  Simultaneous inhibition of GSK3α and GSK3β using hairpin siRNA expression vectors , 2003 .

[108]  E. Marshall Second Child in French Trial Is Found to Have Leukemia , 2003, Science.

[109]  Y. Dong,et al.  Systematic functional analysis of the Caenorhabditis elegans genome using RNAi , 2003, Nature.

[110]  David L. Lewis,et al.  Efficient delivery of siRNA for inhibition of gene expression in postnatal mice , 2002, Nature Genetics.

[111]  K Taira,et al.  siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells , 2003, Nucleic acids research.

[112]  Patrick J. Paddison,et al.  A resource for large-scale RNA-interference-based screens in mammals , 2004, Nature.

[113]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

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

[115]  John J Rossi,et al.  Approaches for the sequence-specific knockdown of mRNA , 2003, Nature Biotechnology.

[116]  R. Medzhitov,et al.  Retroviral delivery of small interfering RNA into primary cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[117]  David A. Williams,et al.  Medicine. Gene therapy--new challenges ahead. , 2003, Science.

[118]  Michael T. McManus,et al.  Gene silencing using micro-RNA designed hairpins. , 2002, RNA.

[119]  M. Martinelli,et al.  Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma. , 2003, Cancer research.

[120]  F. Michiels,et al.  Adenoviral vectors expressing siRNAs for discovery and validation of gene function. , 2003, Genome research.

[121]  V. Kim RNA interference in functional genomics and medicine. , 2003, Journal of Korean medical science.

[122]  I. Verma,et al.  Transgenesis by lentiviral vectors: Lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[123]  Christopher Baum,et al.  Gene Therapy--New Challenges Ahead , 2003, Science.

[124]  D. Engelke,et al.  Effective expression of small interfering RNA in human cells , 2002, Nature Biotechnology.

[125]  W. Gerald,et al.  Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. , 2003, Cancer cell.

[126]  Peter A. Jones,et al.  Establishment of conditional vectors for hairpin siRNA knockdowns. , 2003, Nucleic acids research.

[127]  Andrew G Fraser,et al.  Identification of genes that protect the C. elegans genome against mutations by genome-wide RNAi. , 2003, Genes & development.