Skip to main content
PMC home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2005 Jan 6;25(3):361–381. doi: 10.1002/med.20023

The role of small RNAs in human diseases: Potential troublemaker and therapeutic tools

Huan Gong 1, Chang‐Mei Liu 1, De‐Pei Liu 1,✉, Chih‐Chuan Liang 1
PMCID: PMC7168392  PMID: 15637700

Abstract

Small RNAs, including short interfering RNAs (siRNAs) and microRNAs (miRNAs), are ubiquitous, versatile repressors of gene expression in plants, animals, and many fungi. They can trigger destruction of homologous mRNA or inhibition of cognate mRNA translation and play an important role in maintaining the stable state of chromosome structure and regulating the expression of protein‐coding genes. Furthermore, the recent research showed that there exists close relationship between small RNAs and human diseases. Several human diseases have surfaced in which miRNAs or their machinery might be implicated, such as some neurological diseases and cancers. The specificity and potency of small RNAs suggest that they might be promising as therapeutic agents. This article will review the role of small RNAs in some human diseases etiology and investigations of taking siRNAs as therapeutic tools for treating viral infection, cancer, and other diseases. We also discuss the potential of miRNAs in gene therapy. © 2004 Wiley Periodicals, Inc.

Keywords: small RNAs, short interfering RNAs, microRNAs, RNA interference, gene therapy

REFERENCES

  • 1. Elbashir SM, Lendeckel W, Tusch T. RNA interference is mediated by 21‐ and 22‐nucleotide RNAs. Gene Dev 2001; 15: 188–200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Lagos‐Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001; 294: 853–858. [DOI] [PubMed] [Google Scholar]
  • 3. Lau N, Lim L, Weinstein E, Barte D. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans . Science 2001; 294: 858–862. [DOI] [PubMed] [Google Scholar]
  • 4. Lee R, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans . Science 2001; 294: 862–864. [DOI] [PubMed] [Google Scholar]
  • 5. Agami R. RNAi and related mechanisms and their potential use for therapy. Curr Opin Chem Biol 2002; 6: 829–834. [DOI] [PubMed] [Google Scholar]
  • 6. Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA‐directed nuclease mediates post‐transcriptional gene silencing in Drosophila cells. Nature 2000; 404: 293–296. [DOI] [PubMed] [Google Scholar]
  • 7. Parrish S, Fleenor J, Xu S, Mello C, Fire A. Functional anatomy of a dsRNA trigger: Differential requirement for the two trigger strands in RNA interference. Mol Cell 2000; 6: 1077–1087. [DOI] [PubMed] [Google Scholar]
  • 8. Yang D, Lu H, Erickson JW. Evidence that processed small dsRNAs may mediate sequence‐specific mRNA degradation during RNAi in Drosophila embryos. Curr Biol 2000; 10: 1191–1200. [DOI] [PubMed] [Google Scholar]
  • 9. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: Double‐stranded RNA directs the ATP‐dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000; 101: 25–33. [DOI] [PubMed] [Google Scholar]
  • 10. Olson P, Ambros V. The lin‐4 regulator RNA controls developmental timing in Caenorhabditis elegans by blocking LIN‐14 protein synthesis after the initiation of translation. Dev Biol 1999; 216: 671–680. [DOI] [PubMed] [Google Scholar]
  • 11. Mette MF, Aufsatz W, van der Winden J, Matzke MA, Matzke AJ. Transcriptional silencing and promoter methylation triggered by double‐stranded RNA. EMBO J 2000; 19: 5194–5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Mochizuki K, Fine NA, Fujisawa T, Gorovsky MA. Analysis of a piwi related gene implicates small RNAs in genome rearrangement in tetrahymena. Cell 2002; 110: 689–699. [DOI] [PubMed] [Google Scholar]
  • 13. Plasterk RHA. RNA silencing: The genome 's immune system. Science 2002; 296: 1263–1265. [DOI] [PubMed] [Google Scholar]
  • 14. Vance V, Vaucheret H. RNA silencing in plants—Defense and counterdefense. Science 2001; 292: 2277–2280. [DOI] [PubMed] [Google Scholar]
  • 15. Hannon GJ. RNA interference. Nature 2002; 418: 244–251. [DOI] [PubMed] [Google Scholar]
  • 16. Carrington J, Ambros V. Role of microRNAs in plant and animal development. Science 2003; 30: 336–338. [DOI] [PubMed] [Google Scholar]
  • 17. Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001; 409: 363–366. [DOI] [PubMed] [Google Scholar]
  • 18. Nelson P, Kiriakidou M, Sharma A, Maniataki E, Mourelatos Z. The microRNA world: Small is mighty. Trends Biochem Sci 2003; 28: 534–540. [DOI] [PubMed] [Google Scholar]
  • 19. Novina CD, Sharp PA. The RNAi revolution. Nature 2004; 430: 161–164. [DOI] [PubMed] [Google Scholar]
  • 20. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double‐stranded RNA in Caenorhabditis elegans . Nature 1998; 391: 806–811. [DOI] [PubMed] [Google Scholar]
  • 21. Hamilton A, Voinnet O, Chappell L, Baulcombe D. Two classes of short interfering RNA in RNA silencing. EMBO J 2002; 21: 4671–4679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP. The microRNAs of Caenorhabditis elegans . Gene Dev 2003; 17: 991–1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297. [DOI] [PubMed] [Google Scholar]
  • 24. Lee Y, Ahn C, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, V. Kim N. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425: 415–419. [DOI] [PubMed] [Google Scholar]
  • 25. Yi R, Qin Y, Macara IG, Cullen BR. Exportin‐5 mediates the nuclear export of pre‐microRNAs and short hairpin RNAs. Gene Dev 2003; 17: 3011–3016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science 2004; 303: 95–98. [DOI] [PubMed] [Google Scholar]
  • 27. Hutvágner G, McLachlan J, Pasquinelli A, Bálint E, Tuschl T, Zamore PD. A cellular function for the RNA‐interference enzyme Dicer in the maturation of the let‐7 small temporal RNA. Science 2001; 293: 834–838. [DOI] [PubMed] [Google Scholar]
  • 28. Grishok A, Pasquinelli A, Conte D, Li N, Parrish S, Ha I, Baillie D, Fire A, Ruvkun G, Mello C. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans and developmental timing. Cell 2001; 106: 23–34. [DOI] [PubMed] [Google Scholar]
  • 29. Llave C, Xie Z, Kasschau K, Carrington J. Cleavage of scarecrow‐like mRNA targets directed by a class of Arabidopsis miRNA. Science 2002; 297: 2053–2056. [DOI] [PubMed] [Google Scholar]
  • 30. Kasschau K, Xie Z, Allen E, Llave C, Chapman E, Krizan K, Carrington J. P1/HC‐Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA function. Dev Cell 2003; 4: 205–217. [DOI] [PubMed] [Google Scholar]
  • 31. Boutet S, Vasquez F, Liu J, Béclin C, Fagard M, Gratias A, Morel JB, Crété P, Chen X, Vaucheret H. Arabidopsis HEN1: A genetic link between endogenous miRNA controlling development and siRNA controlling transgene silencing and virus resistance. Curr Biol 2003; 13: 843–848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Johnston RJ, Hobert OA. MicroRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans . Nature 2003; 426: 845–849. [DOI] [PubMed] [Google Scholar]
  • 33. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83–86. [DOI] [PubMed] [Google Scholar]
  • 34. Okamura K, Ishizuka A, Siomi H, Siomi MC. Distinct roles for Argonaute proteins in small RNA‐directed RNA cleavage pathways. Genes Dev 2004; 18: 1655–1666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Carmell MA, Xuan Z, Zhang MQ, Hannon GJ. The Argonaute family: Tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Gene Dev 2002; 16: 2733–2742. [DOI] [PubMed] [Google Scholar]
  • 36. Lim L, Glasner M, Yekta S, Burge C, Bartel D. Vertebrate microRNA genes. Science 2003; 299: 1540. [DOI] [PubMed] [Google Scholar]
  • 37. Caudy AA, Myers M, Hannon GJ, Hammond SM. Fragile X‐related protein and VIG associate with the RNA interference machinery. Gene Dev 2002; 16: 2491–2496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Ishizuka A, Siomi MC, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Gene Dev 2002; 16: 2497–2508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Bardoni B, Mandel JL. Advances in understanding of fragile X pathogenesis and FMRP function and in identification of X linked mental retardation genes. Curr Opin Genet Dev 2002; 12: 284–293. [DOI] [PubMed] [Google Scholar]
  • 40. Carthew RW. RNA interference: The fragile X syndrome connection. Curr Biol 2002; 12: R852–R854. [DOI] [PubMed] [Google Scholar]
  • 41. Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J, Jongens TA, Nelson DL, Moses K, Warren ST. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci 2004; 7: 113–117. [DOI] [PubMed] [Google Scholar]
  • 42. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G. miRNPs: A novel class of ribonucleoproteins containing numerous micro‐RNAs. Genes Dev 2002; 16: 720–728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular characterization of hiwi: A human member of the piwi gene family whose overexpression is correlated to eminomas. Oncogene 2002; 21: 3988–3999. [DOI] [PubMed] [Google Scholar]
  • 44. Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 2003; 9: 180–186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down‐regulation of micro‐RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524–15529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Dong JT, Boyd JC, Frierson HF, Jr . Loss of heterozygosity at 13q14 and 13q21 in high grade, high‐stage prostate cancer. Prostate 2001; 49: 166–171. [DOI] [PubMed] [Google Scholar]
  • 47. Lagos‐Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue‐specific microRNAs from mouse. Curr Biol 2002; 12: 735–739. [DOI] [PubMed] [Google Scholar]
  • 48. Michael MZ, O'Connor SM, Pellekaan NGH, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003; 1: 882–891. [PubMed] [Google Scholar]
  • 49. Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A. High expression of precursor microRNA‐155/BIC RNA in children with Burkitt lymphoma. Gene Chromosome Cancer 2004; 39: 167–169. [DOI] [PubMed] [Google Scholar]
  • 50. Hutvagner G, Zamore PD. A microRNA in a multiple‐turnover RNAi enzyme complex. Science 2002; 297: 2056–2060. [DOI] [PubMed] [Google Scholar]
  • 51. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999–3004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Ambros V. MicroRNAs: Tiny regulators with great potential. Cell 2001; 107: 823–826. [DOI] [PubMed] [Google Scholar]
  • 53. Storz G. An expanding universe of noncoding RNAs. Science 2002; 296: 1260–1263. [DOI] [PubMed] [Google Scholar]
  • 54. Schwarz DS, Zamore PD. Why do miRNAs live in the miRNP? Genes Dev 2002; 16: 1025–1031. [DOI] [PubMed] [Google Scholar]
  • 55. McManus MT. MicroRNAs and cancer. Semin Cancer Biol 2003; 13: 253–258. [DOI] [PubMed] [Google Scholar]
  • 56. Martínez MA, Gutiérrez A, Armand‐Upón M, Blanco J, Parera M, Gómez J, Clotet B, Esté JA. Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV‐1 replication. AIDS 2002; 16: 2385–2390. [DOI] [PubMed] [Google Scholar]
  • 57. Coburn GA, Cullen BR. Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 2002; 76: 9225–9231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58. Novina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, Collman RG, Lieberman J, Shankar P, Sharp PA. siRNA‐directed inhibition of HIV‐1 infection. Nat Med 2002; 8: 681–686. [DOI] [PubMed] [Google Scholar]
  • 59. Sholmai A, Shaul Y. Inhibition of hepatitis B virus expression and replication by RNA interference. Hepatology 2003; 37: 764–770. [DOI] [PubMed] [Google Scholar]
  • 60. Randall G, Grakoui A, Rice CM. Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs. Proc Natl Acad Sci USA 2003; 100: 235–240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61. Jiang M, Milner J. Selective silencing of viral gene expression in HPV‐positive human cervical carcinoma cells treatment with siRNA: A primer of RNA interference. Oncogene 2002; 21: 6041–6048. [DOI] [PubMed] [Google Scholar]
  • 62. Ge Q, McManus MT, Nguyen T, Shen CH, Sharp PA, Eisen HN, Chen J. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci USA 2003; 100: 2718–2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J. Inhibition of influenza virus production in virus‐infected mice by RNA interference. Proc Natl Acad Sci USA 2004; 101: 8676–8681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64. Tompkins SM, Lo CY, Tumpey TM, Epstein SL. Protection against lethal influenza virus challenge by RNA interference in vivo . Proc Natl Acad Sci USA 2004; 101: 8682–8686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65. Zhang Y, Li T, Fu L, Yu C, Li Y, Xu X, Wang Y, Ning H, Zhang S, Chen W, Babiuk LA, Chang Z. Silencing SARS‐CoV Spike protein expression in cultured cells by RNA interference. FEBS Lett 2004; 560: 141–146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Wang Z, Ren L, Zhao X, Hung T, Meng A, Wang J, Chen YG. Inhibition of severe acute respiratory syndrome virus replication by small interfering RNAs in mammalian cells. J Virol 2004; 78: 7523–7527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67. Cioca DP, Aoki Y, Kiyosawa K. RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer Gene The 2003; 10: 125–133. [DOI] [PubMed] [Google Scholar]
  • 68. Spankuch B, Matthess Y, Knecht R, Zimmer B, Kaufmann M, Strebhardt K. Cancer inhibition in nude mice after systemic application of U6 promoter‐driven short hairpin RNAs against PLK1. J Natl Cancer Inst 2004; 96: 862–872. [DOI] [PubMed] [Google Scholar]
  • 69. Wilda M, Fuchs U, Wossmann W, Borkhardt A. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi). Oncogene 2002; 21: 5716–5724. [DOI] [PubMed] [Google Scholar]
  • 70. Scherr M, Battmer K, Winkler T, Heidenreich O, Ganser A, Eder M. Specific inhibition of bcr‐abl gene expression by small interfering RNA. Blood 2003; 101: 1566–1569. [DOI] [PubMed] [Google Scholar]
  • 71. Brummelkamp TR, Bernards R, Agami R. Stable suppression of tumorigenicity by virus‐mediated RNA interference. Cancer Cell 2002; 2: 243–247. [DOI] [PubMed] [Google Scholar]
  • 72. Nieth C, Priebsch A, Stege A, Lage H. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett 2003; 545: 144–150. [DOI] [PubMed] [Google Scholar]
  • 73. Yague E, Higgins CF, Raguz S. Complete reversal of multidrug resistance by stable expression of small interfering RNAs targeting MDR1. Gene Ther 2004; 11: 1170–1174. [DOI] [PubMed] [Google Scholar]
  • 74. Peng Y, Zhang Q, Nagasawa H, Okayasu R, Liber HL, Bedford JS. Silencing expression of the catalytic subunit of DNA‐dependent protein kinase by small interfering RNA sensitizes human cells for radiation‐induced chromosome damage, cell killing, and mutation. Cancer Res 2002; 62: 6400–6404. [PubMed] [Google Scholar]
  • 75. Chen J, Wall NR, Kocher K, Duclos N, Fabbro D, Neuberg D, Griffin JD, Shi Y, Gilliland DG. Stable expression of small interfering RNA sensitizes TEL‐PDGFbetaR to inhibition with imatinib or rapamycin. J Clin Invest 2004; 113: 1784–1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Lipscomb EA, Dugan AS, Rabinovitz I, Mercurio AM. Use of RNA interference to inhibit integrin mediated invasion and migration of breast carcinoma cells. Clin Exp Metastas 2003; 20: 569–576. [DOI] [PubMed] [Google Scholar]
  • 77. Salvi A, Arici B, De Petro G, Barlati S. Small interfering RNA urokinase silencing inhibits invasion and migration of human hepatocellular carcinoma cells. Mol Cancer Ther 2004; 3: 671–678. [PubMed] [Google Scholar]
  • 78. Xia H, Mao Q, Eliason SL, Harper SQ, Martins IH, Orr HT, Paulson HL, Yang L, Kotin RM, Davidson BL. RNAi suppresses polyglutamine‐induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 2004; 10: 816–820. [DOI] [PubMed] [Google Scholar]
  • 79. Caplen NJ, Taylor JP, Statham VS, Tanaka F, Fire A, Morgan RA. Rescue of polyglutamine‐mediated cytoxicity by double‐stranded RNA‐mediated RNA interference. Hum Mol Genet 2002; 11: 175–184. [DOI] [PubMed] [Google Scholar]
  • 80. McCaffrey AP, Nakai H, Pandey K, Huang Z, Salazar FH, Xu H, Wieland SF, Marion PL, Kay MA. Inhibition of hepatitis B virus in mice by RNA interference. Nat Biotechnol 2003; 21: 639–644. [DOI] [PubMed] [Google Scholar]
  • 81. Konishi M, Wu CH, Wu GY. Inhibition of HBV repliation by siRNA in a stable HBV‐producing cell line. Hepatology 2003; 38: 842–850. [DOI] [PubMed] [Google Scholar]
  • 82. McCaffrey AP, Meuse L, Karimi M, Contag CH, Kay MA. A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice. Hepatology 2003; 38: 503–508. [DOI] [PubMed] [Google Scholar]
  • 83. Jacque JM, Triques K, Stevenson M. Modulation of HIV‐1 replication by RNA interference. Nature 2002; 418: 435–438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84. Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, Salvaterra P, Rossi J. Expression of small interfering RNAs targeted against HIV‐1 rev transcripts in human cells. Nat Biotechnol 2002; 20: 500–505. [DOI] [PubMed] [Google Scholar]
  • 85. Martínez MA, Clotet B, Esté JA. RNA interference of HIV replication. Trends Immunol 2002; 23: 559–561. [DOI] [PubMed] [Google Scholar]
  • 86. Qin XF, An DS, Chen IS, Baltimore D. Inhibiting HIV‐1 infection in human T cells by lentiviral‐mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA 2003; 100: 183–188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87. Gitllin L, Karelsky S, Andino R. Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 2002; 418: 430–434. [DOI] [PubMed] [Google Scholar]
  • 88. Miller VM, Xia H, Marrs GL, Gouvion CM, Lee G, Davidson BL, Paulson HL. Allele‐specific silencing of dominant disease genes. Proc Natl Acad Sci USA 2003; 100: 7195–7200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89. Brantl S. Antisense‐RNA regulation and RNA interference. Biochim Biophys Acta 2002; 1575: 15–25. [DOI] [PubMed] [Google Scholar]
  • 90. Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002; 296: 550–553. [DOI] [PubMed] [Google Scholar]
  • 91. Lieberman J, Song E, Lee SK, Shankar P. Interfering with disease: Opportunities and roadblocks to harnessing RNA interference. Trends Mol Med 2003; 9: 397–403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA 2003; 100: 9779–9784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 2002; 9: 1–20. [DOI] [PubMed] [Google Scholar]
  • 94. Hemann MT, Fridman JS, Zilfou JT, Hernando E, Patrick PJ, Cordon‐Cardo C, Hannon GJ, Lowe SW. An epi‐allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo . Nat Genet 2003; 33: 396–400. [DOI] [PubMed] [Google Scholar]
  • 95. Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Zhang M, McManus MT, Gertler FB, Scott ML, Parijs LV. A lentivirus‐based system to functionally silence genes in primary mammalian cells, stem cells, and transgenic mice by RNA interference. Nat Genet 2003; 33: 401–406. [DOI] [PubMed] [Google Scholar]
  • 96. Wetering M, Oving I, Muncan V, Fong MTP, Brantjes H, Leenen D, Holstege FCP, Brummelkamp TR, Agami R, Clevers H. Specific inhibition of gene expression using a stably integrated, inducible small‐interfering‐RNA vector. EMBO R 2003; 4: 609–615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97. Wiznerowicz M, Trono D. Conditional suppression of cellular genes: Lentivirus vector‐mediated drug‐inducible RNA interference. J Virol 2003; 77: 8957–8961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98. Matsukura S, Jones PA, Takai D. Establishment of conditional vectors for hairpin siRNA knockdowns. Nucleic Acids Res 2003; 31: e77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99. Gupta S, Schoer RA, Egan JE, Hannon GJ, Mittal V. Inducible, reversible, and stable RNA interference in mammalian cells. Proc Natl Acad Sci USA 2004; 101: 1927–1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100. Tiscornia G, Tergaonkar V, Galimi F, Verma IM. CRE recombinase‐inducible RNA interference mediated by lentiviral vectors. Proc Natl Acad Sci USA 2004; 101: 7347–7351. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Medicinal Research Reviews are provided here courtesy of Wiley

RESOURCES