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siRNA Efficiency: Structure or Sequence—That Is the Question

By Jens Kurreck


The triumphant success of RNA interference (RNAi) in life sciences is based on its high potency to silence genes in a sequence-specific manner. Nevertheless, the first task for successful RNAi approaches is the identification of highly active small interfering RNAs (siRNAs). Early on, it has been found that the potency of siRNAs can vary drastically. Great progress was made when thermodynamic properties that influence siRNA activity were discovered. Design algorithms based on these parameters enhance the chance to generate potent siRNAs. Still, many siRNAs designed accordingly fail to silence their targeted gene, whereas others are highly efficient despite the fact that they do not fulfil the recommended criteria. Therefore, the accessibility of the siRNA-binding site on the target RNA has been investigated as an additional parameter which is important for RNAi-mediated silencing. These and other factors which are crucial for successful RNAi approaches will be discussed in the present review

Topics: Review Article
Publisher: Hindawi Publishing Corporation
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Provided by: PubMed Central
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    1. (2005). A lentiviral microRNA-based system for single-copy polymerase II-regulatedRNAinterferenceinmammaliancells.Proceedings oftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.
    2. A protein sensorfor siRNA asymmetry.
    3. An algorithm for selection of functional siRNA sequences.
    4. An endoribonucleaseprepared siRNA screen in human cells identifies genes essential for cell division.
    5. Analysis of gene function in somatic mammalian cells using small interfering RNAs.
    6. Antisense that comes naturally.
    7. Argonaute2 is the catalytic engine of mammalian RNAi.
    8. (2002). Comparison of antisense oligonucleotides and siRN A si nc e l lc u l t u r ea n di nv i v o .Biochemical and Biophysical Research Communications.
    9. Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2’O-methyl RNA, phosphorothioates and small interfering RNA.
    10. (2003). Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells. Antisense and Nucleic Acid Drug Development.
    11. Crystal structure of argonaute and its implications for RISC slicer activity.
    12. Design of a genomewide siRNA library using an artificial neural network.
    13. Design of siRNAs producing unstructured guideRNAs results in improved RNA interference efficiency.
    14. Designer siRNAs to overcome the challenges in a stolen natural process.
    15. Developing an effective RNA interference strategy against a plus-strand RNA virus: silencing of coxsackievirus B3 and its cognate coxsackievirusadenovirus receptor.
    16. DNAzymes and small interfering RNAs as therapeutics. Current Drug Targets.
    17. (2003). Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. J o u r n a lo fB i -ological Chemistry.
    18. Functional polarity is introduced by Dicer processing of short substrate RNAs.
    19. Functional siRNAs and miRNAs exhibit strand bias.
    20. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference.
    21. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.
    22. Improved and automated prediction of effective siRNA.
    23. Inhibition of Coxsackievirus B3 replication by small interfering RNAs requires perfect sequence match in the central region of the viral positive strand.
    24. Kretschmer-KazemiFarR,SczakielG.TheactivityofsiRNAin mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides.
    25. Local RNA target structure influences siRNA efficacy: a systematic global analysis.
    26. Local RNA target structure influences siRNA efficacy: systematic analysis of intentionally designed binding regions.
    27. Maintaining inhibition: siRNA double expression vectors against coxsackieviral RNAs.
    28. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes.
    29. Positional effects of short interfering RNAs targeting the human coagulationtriggerTissueFactor.NucleicAcidsResearch.2002;
    30. Purified Argonaute2 and an siRNA form recombinant human RISC.
    31. R a n dT A ,P e t e r s e nS ,D uF ,W a n gX .A r g o n a u t e 2c l e a v e s the anti-guide strand of siRNA during RISC activation.
    32. Rational siRNA design for RNA interference.
    33. (2005). RNA interference as a genespecific approach for molecular medicine. Current Medicinal Chemistry.
    34. (2003). RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells.
    35. (2005). RNA interference: from gene silencing to gene-specific therapeutics. Pharmacology and Therapeutics.
    36. S a n d yP ,V e n t u r aA ,J a c k sT .M a m m a l i a nR N A i :ap r a c t i c a l guide.
    37. Second-generation shRNA libraries covering the mouse and human genomes.
    38. sequence and position of the targeted region.
    39. Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Research. 2004;32(web server issue):W135–W141.
    40. siRNA design including secondary structure target site prediction. Nature Methods. 2005;2(8):1– 2. application note.
    41. (2005). siRNA therapeutics: big potential from small RNAs. Gene Therapy.
    42. Small interfering RNA molecules as potential anti-human rhinovirus agents: in vitro potency, specificity, and mechanism.
    43. (2005). Small non-coding RNAs as magic bullets. Trends in Biochemical Sciences.
    44. (2005). Small RNA asymmetry in RNAi: function in RISC assembly and gene regulation. FEBS Letters.
    45. Structural basis for doublestranded RNA processing by Dicer.
    46. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy.
    47. Synthetic shRNAs as potent RNAi triggers.
    48. (2005). Target accessibility dictates the potency of human RISC. Nature Structural and Molecular Biology.
    49. 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.
    50. (2004). The functions of animal microRNAs.
    51. The gene-silencing efficiency of siRNA is strongly dependent on the local structure of mRNA at the targeted region.
    52. The prospect of silencing disease using RNA interference.
    53. The therapeutic potential of RNA interference.
    54. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing.
    55. TuschlT.Duplexesof21-nucleotideRNAsmediateRNAinterference in cultured mammalian cells.

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