Orvosi Hetilap
Volume/Issue:
Volume 148: Issue 47
RNA interference and its clinical applications
Authors: Gyöngyi Munkácsy 1 , Zsolt Tulassay, and Balázs Győrffy 1
View More View Less
  • 1 MTA-SE Gyermekgyógyászati és Nephrológiai Kutatócsoport Budapest Bókay u. 53–54. 1083
  • 2 Semmelweis Egyetem, Általános Orvostudományi Kar II. Belgyógyászati Klinika Budapest
  • 3 MTA-SE Molekuláris Medicina Kutatócsoport Budapest
DOI:
https://doi.org/10.1556/oh.2007.28199
Page Count:
2235–2240
Publication Date:
01 Nov 2007
Online Publication Date:
14 Nov 2007
Article Category:
Research Article
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $1,070.00
Purchase Online Subscription

  • Purchase article

    USD  $25.00

  • 1 year subscription (Individual Only)

    USD  $1,070.00

Az RNS-interferencia a poszttranszkripciós génelcsendesítés olyan formája, amelynek során rövid, specifikusan RNS-molekulák elnyomják a gének kifejeződésében kulcsszerepet játszó hírvivő RNS-ek működését. A sejtbe juttatott dupla szálú vagy rövid interferáló RNS-molekulák aktiválják az RNS-indukált elcsendesítő komplexet, amely a célgén hírvivő RNS-ét lebontja. A sejtek saját szabályozó mikro-RNS-molekulákkal is rendelkeznek, amelyeknek hírvivő RNS-e képes önmagával hajtűt képezni, amit a sejt dupla szálú RNS-ként értelmez. Az RNS-interferencia élettani működései közé tartozik a vírusok és a transzpozonok elleni védekezés, valamint a génkifejeződés szabályozása. Az RNS-interferencia nemcsak in vitro alkalmazható az egyes gének működésének vizsgálatára, hanem klinikai alkalmazásainak lehetőségei is megjelentek. Eddig vírusfertőzésekben, az időskori makuladegeneráció gátlására, a vér koleszterinszint-csökkentésére, daganatellenes és neurodegeneratív betegségek kezelésében alkalmazták. Az RNS-interferencia alkalmazását azonban nehezíti, hogy a megfelelő rövid interferáló RNS-molekulák tervezéséhez szükséges bioinformatikai algoritmusok nem tökéletesek; a szervezet szöveteibe való bejuttatásuk nehéz; illetve csak olyan esetekben alkalmazható, amelyekben átmeneti antagonista génelcsendesítő hatás és nem hosszú távú kezelés szükséges. Az alkalmazás legnagyobb előnye a jelentős specificitás, ami miatt mellékhatása is kevés. Az RNS-interferencia alapú kezelések megjelenése már a közeli jövőben várható.

  • Fire, A., Xu, S. Q., Montgomery, M. K. és mtsai: Potent and specific genetic interference by doublestranded RNA in Caenorhabditis elegans . Nature, 1998, 391 , 806–811.

    Montgomery M. K. , 'Potent and specific genetic interference by doublestranded RNA in Caenorhabditis elegans ' (1998 ) 391 Nature : 806 -811.

    • Search Google Scholar

  • Vaucheret, H., Béclin, C., Elmayan, T. és mtsai: Transgene-induced gene silencing in plants. The Plant Journal, 1998, 16 , 651–659.

    Elmayan T. , 'Transgene-induced gene silencing in plants ' (1998 ) 16 The Plant Journal : 651 -659.

    • Search Google Scholar

  • Napoli, C., Lemieux, C., Jorgensen, R.: Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous gene in trans . Plant Cell, 1990, 2 , 279–289.

    Jorgensen R. , 'Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous gene in trans ' (1990 ) 2 Plant Cell : 279 -289.

    • Search Google Scholar

  • van der Krol, A. R., Mur, L. A., Beld, M. és mtsai: Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell, 1990, 2 , 291–299.

    Beld M. , 'Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression ' (1990 ) 2 Plant Cell : 291 -299.

    • Search Google Scholar

  • Romano, N., Macino, G.: Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Mol. Microbiol., 1992, 6 , 3343–3353.

    Macino G. , 'Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences ' (1992 ) 6 Mol. Microbiol. : 3343 -3353.

    • Search Google Scholar

  • Cogoni, C., Irelan, J. T., Schumacher, M. és mtsai: 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. EMBO J., 1996, 15 , 3153–3163.

    Schumacher M. , '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 ) 15 EMBO J. : 3153 -3163.

    • Search Google Scholar

  • Timmons, L., Fire, A.: Specific interference by ingested dsRNA. Nature, 1998, 395 , 854.

    Fire A. , 'Specific interference by ingested dsRNA ' (1998 ) 395 Nature : 854 -.

  • Rocheleau, C. E., Downs, W. D., Lin, R. és mtsai: Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell, 1997, 90 , 707–716.

    Lin R. , 'Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos ' (1997 ) 90 Cell : 707 -716.

    • Search Google Scholar

  • Sharp, P. A.: RNAi and double-strand RNA. Genes Dev., 1999, 13 , 139–141.

    Sharp P. A. , 'RNAi and double-strand RNA ' (1999 ) 13 Genes Dev. : 139 -141.

  • Bernstein, E., Caudy, A. A., Hammond, S. M. és mtsa: Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 2001, 409 , 363–366.

    Hammond S. M. , 'Role for a bidentate ribonuclease in the initiation step of RNA interference ' (2001 ) 409 Nature : 363 -366.

    • Search Google Scholar

  • Hammond, S. M., Bernstein, E., Beach, D. és mtsa: An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature, 2000, 404 , 293–296.

    Beach D. , 'An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells ' (2000 ) 404 Nature : 293 -296.

    • Search Google Scholar

  • Fire, A.: RNA-triggered gene silencing. Trends Genet., 1999, 15 , 358–363.

    Fire A. , 'RNA-triggered gene silencing ' (1999 ) 15 Trends Genet. : 358 -363.

  • Rácz Zs., Hamar P.: Can siRNA Technology Provide the Tools for Gene Therapy of the Future? Curr. Med. Chem., 2006, 13 , 2299–2307.

    Hamar P. , 'Can siRNA Technology Provide the Tools for Gene Therapy of the Future? ' (2006 ) 13 Curr. Med. Chem. : 2299 -2307.

    • Search Google Scholar

  • Waterhouse, P. M., Graham, M. W., Wang, M. B.: Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proc. Natl. Acad. Sci., 1998, 95 , 13959–13964.

    Wang M. B. , 'Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA ' (1998 ) 95 Proc. Natl. Acad. Sci. : 13959 -13964.

    • Search Google Scholar

  • Kumar, M., Carmichael, G. G.: Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes. Microbiol. Mol. Biol. Rev., 1998, 62 , 1415–1434.

    Carmichael G. G. , 'Antisense RNA: Function and Fate of Duplex RNA in Cells of Higher Eukaryotes ' (1998 ) 62 Microbiol. Mol. Biol. Rev. : 1415 -1434.

    • Search Google Scholar

  • Sijen, T., Plasterk, R. H. A.: Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature, 2003, 426 , 310–314.

    Plasterk R. H. A. , 'Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi ' (2003 ) 426 Nature : 310 -314.

    • Search Google Scholar

  • Affar, el B., Gay, F., Shi, Y. és mtsai: Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell cycle progression. Mol. Cell. Biol., 2006, 26 , 3565–3581.

    Shi Y. , 'Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell cycle progression ' (2006 ) 26 Mol. Cell. Biol. : 3565 -3581.

    • Search Google Scholar

  • Engels, B. M., Hutvagner, G.: Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene, 2006, 25 , 6163–6169.

    Hutvagner G. , 'Principles and effects of microRNA-mediated post-transcriptional gene regulation ' (2006 ) 25 Oncogene : 6163 -6169.

    • Search Google Scholar

  • Ngo, H., Tschudi, C., Gull, K. és mtsa: Double-stranded RNA induces mRNA degradation in Trypanosoma brucei . Proc. Nat. Acad. Sci. USA, 1998, 95 , 14687–14692.

    Gull K. , 'Double-stranded RNA induces mRNA degradation in Trypanosoma brucei ' (1998 ) 95 Proc. Nat. Acad. Sci. USA : 14687 -14692.

    • Search Google Scholar

  • Kennerdell, J. R., Carthew, R. W.: Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell, 1998, 95 , 1017–1026.

    Carthew R. W. , 'Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway ' (1998 ) 95 Cell : 1017 -1026.

    • Search Google Scholar

  • Wianny, F., Zernicka-Goetz, M.: Specific interference with gene function by double-stranded RNA in early mouse development. Nat. Cell. Biol., 2000, 2 , 70–75.

    Zernicka-Goetz M. , 'Specific interference with gene function by double-stranded RNA in early mouse development ' (2000 ) 2 Nat. Cell. Biol. : 70 -75.

    • Search Google Scholar

  • Elbashir, S. M., Harborth, J., Lendeckel, W. és mtsai: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 2001, 411 , 494–498.

    Lendeckel W. , 'Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells ' (2001 ) 411 Nature : 494 -498.

    • Search Google Scholar

  • Bumcrot, D., Manoharan, M., Koteliansky, V. és mtsa: RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol., 2006, 2 , 711–719.

    Koteliansky V. , 'RNAi therapeutics: a potential new class of pharmaceutical drugs ' (2006 ) 2 Nat. Chem. Biol. : 711 -719.

    • Search Google Scholar

  • MacKeigan, J. P., Murphy, L. O., Blenis, J.: Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat. Cell. Biol., 2005, 7 , 591–600.

    Blenis J. , 'Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance ' (2005 ) 7 Nat. Cell. Biol. : 591 -600.

    • Search Google Scholar

  • Pulukuri, S. M. K., Gondi, C. S., Lakka, S. S. és mtsai: RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo . J. Biol. Chem., 2005, 280 , 36529–36540.

    Lakka S. S. , 'RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo ' (2005 ) 280 J. Biol. Chem. : 36529 -36540.

    • Search Google Scholar

  • Gurzov, E. N., Izquierdo, M.: RNA interference against Hec1 inhibits tumor growth in vivo. Gene Ther., 2006, 13 , 1–7.

    Izquierdo M. , 'RNA interference against Hec1 inhibits tumor growth in vivo ' (2006 ) 13 Gene Ther. : 1 -7.

    • Search Google Scholar

  • Hu-Lieskovan, S., Heidel, J. D., Bartlett, D. W. és mtsai: Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’s sarcoma. Cancer Res., 2005, 65 , 8984–8992.

    Bartlett D. W. , 'Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’s sarcoma ' (2005 ) 65 Cancer Res. : 8984 -8992.

    • Search Google Scholar

  • Landen, C. N. Jr., Chavez-Reyes, A., Bucana, C. és mtsai: Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res., 2005, 65 , 6910–6918.

    Bucana C. , 'Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery ' (2005 ) 65 Cancer Res. : 6910 -6918.

    • Search Google Scholar

  • Pai, S. I., Lin, Y-Y., Macaes, B. és mtsai: Prospects of RNA interference therapy for cancer. Gene Ther., 2006, 13 , 464–477.

    Macaes B. , 'Prospects of RNA interference therapy for cancer ' (2006 ) 13 Gene Ther. : 464 -477.

    • Search Google Scholar

  • Soutschek, J., Akinc, A., Bramlage, B.: Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature, 2004, 432 , 173–178.

    Bramlage B. , 'Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs ' (2004 ) 432 Nature : 173 -178.

    • Search Google Scholar

  • Ratcliff, F., Harrison, B., Baulcombe, D.: A similarity between viral defense and gene silencing in plants. Science, 1997, 276 , 1558–1560.

    Baulcombe D. , 'A similarity between viral defense and gene silencing in plants ' (1997 ) 276 Science : 1558 -1560.

    • Search Google Scholar

  • Vaucheret, H., Béclin, C., Fagard, M.: Post-transcriptional gene silencing in plants. J. Cell Sci., 2001, 114 , 3083–3091.

    Fagard M. , 'Post-transcriptional gene silencing in plants ' (2001 ) 114 J. Cell Sci. : 3083 -3091.

    • Search Google Scholar

  • Tan, E. L., Tan, T. M., Chow, V. T. és mtsai: Enhanced potency and efficacy of 29-mer shRNAs in inhibition of Enterovirus 71. Antiviral Res., 2007, 74 , 9–15.

    Chow V. T. , 'Enhanced potency and efficacy of 29-mer shRNAs in inhibition of Enterovirus 71 ' (2007 ) 74 Antiviral Res. : 9 -15.

    • Search Google Scholar

  • Jacque, J. M., Triques, K., Stevenson, M.: Modulation of HIV-1 replication by RNA interference. Nature, 2002, 418 , 435–438.

    Stevenson M. , 'Modulation of HIV-1 replication by RNA interference ' (2002 ) 418 Nature : 435 -438.

    • Search Google Scholar

  • Rossi, J. J.: RNAi as a treatment for HIV-1 infection. Biotechniques, 2006, 52 , 25–29.

    Rossi J. J. , 'RNAi as a treatment for HIV-1 infection ' (2006 ) 52 Biotechniques : 25 -29.

  • Yang, L., Kotin, R. M., Davidson, B. L., és mtsai: Selective inhibition of hepatitis B virus replication by RNA interference. Biochem. Biophys. Res. Commun., 2003, 309 , 482–484.

    Davidson B. L. , 'Selective inhibition of hepatitis B virus replication by RNA interference ' (2003 ) 309 Biochem. Biophys. Res. Commun. : 482 -484.

    • Search Google Scholar

  • Ge, Q., McManus, M. T., Nguyen, T. és mtsai: 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.

    Nguyen T. , 'RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription ' (2003 ) 100 Proc. Natl. Acad. Sci. USA : 2718 -2723.

    • Search Google Scholar

  • Xia, H., Mao, Q., Eliason, S. L. és mtsai: RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med., 2004, 10 , 816–820.

    Eliason S. L. , 'RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia ' (2004 ) 10 Nat. Med. : 816 -820.

    • Search Google Scholar

  • Raoul, C., Barker, S. D., Aebischer, P.: Viral-based modelling and correction of neurodegenerative diseases by RNA interference. Gene Ther., 2006, 13 , 487–495.

    Aebischer P. , 'Viral-based modelling and correction of neurodegenerative diseases by RNA interference ' (2006 ) 13 Gene Ther. : 487 -495.

    • Search Google Scholar

  • Tuschl, T., Zamore, P. D., Lehmann, R. és mtsai: Targeted mRNA degradation by double-stranded RNA in vitro. Genes Dev., 1999, 13 , 3191–3197.

    Lehmann R. , 'Targeted mRNA degradation by double-stranded RNA in vitro ' (1999 ) 13 Genes Dev. : 3191 -3197.

    • Search Google Scholar

  • Snøve, O., Nedland, M., Fjeldstad, S. H. és mtsai: Designing effective siRNAs with off-target control. Biochem. Biophys. Res. Commun., 2004, 325 , 769–773.

    Fjeldstad S. H. , 'Designing effective siRNAs with off-target control ' (2004 ) 325 Biochem. Biophys. Res. Commun. : 769 -773.

    • Search Google Scholar
Cover Orvosi Hetilap
Orvosi Hetilap
Print ISSN:
0030-6002
Online ISSN:
1788-6120
Keywords:
RNS-interferencia; daganatterápia; vírusfertőzés; makuladegeneráció; hypercholesterinaemia; RNA interference; cancer therapy; viral infection; macula degeneration; hipercholesterinaemia

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Nov 2020 14 1 0
Dec 2020 33 0 1
Jan 2021 23 0 3
Feb 2021 18 0 0
Mar 2021 29 0 0
Apr 2021 10 0 0
May 2021 0 0 0