Chemical modification of siRNAs to improve serum stability without loss of efficacy

Choung, Sorim; Kim, Young Joo; Kim, Seonhoe; Park, Han-Oh; Choi, Young‐Chul

doi:10.1016/j.bbrc.2006.02.049

Cited by 300 publications

(211 citation statements)

References 31 publications

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“…Incorporation of 2′-O-methyl modifications is an efficient and inexpensive method to improve nuclease resistance of synthetic RNA duplexes [33,[37][38][39][40]. However, dsiRNA duplexes with modifications of all or the majority of nucleotides in both sense and antisense strands are practically inactive, because extensive modification blocks the cleavage of duplex by Dicer [17].…”

Section: Dicer Substrate Interfering Rnasmentioning

confidence: 99%

Noncanonical Synthetic RNAi Inducers

Gvozdeva¹,

Chernolovskaya²

2016

RNA Interference

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This review focuses on current strategies of development of noncanonical synthetic RNA interference (RNAi) inducers with structural modifications for promoting better gene silencing with low risk of side effects. A particular focus is on longer RNA duplexes 25-30 nucleotides (nt) in length that mimic Dicer substrates to improve interaction of RNAi inducers with RNAi machinery. Various design strategies of efficient Dicer substrate smallinterfering RNA (siRNA) are described. It was found that the length, chemical modifications, and overhang structure influence the gene silencing activity and RNA-induced silencing complex (RISC) assembly. Special attention is paid to the long doublestranded RNA duplexes that induce effective gene silencing in Dicer-dependent or Dicerindependent mode. Some structural variants of shorter siRNAs, including hairpin and dumbbell siRNAs and fork-siRNA (fsiRNA) with several nucleotide substitutions at the 3′ end of the sense strand, are also analyzed. These structural modifications provide efficiently increased gene silencing of targets with unfavorable duplex thermodynamic asymmetry. Recent data remove the length and structure limits for the design of RNAi effectors, and add another example in the list of novel RNAi-inducing molecules differing from the classical siRNA, which is discussed in this chapter.

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Section: Dicer Substrate Interfering Rnasmentioning

confidence: 99%

Noncanonical Synthetic RNAi Inducers

Gvozdeva¹,

Chernolovskaya²

2016

RNA Interference

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“…The increase of the number of modifications was shown to decrease the silencing activity of siRNAs; totally modified siRNAs frequently had no activity [58,59,71]. However, in a number of experiments the activity of siRNA with the totally modified sense strand was compatible with that of unmodified analog [72,73]. This can be related to functional unequivalence of siRNA strands [74,75].…”

Section: Substituents In Furanosementioning

confidence: 99%

Structure - Functions Relations in Small Interfering RNAs

Petrova¹,

Зенкова²,

Chernolovskaya³

2013

Practical Applications in Biomedical Engineering

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“…Certain chemical modifications can be introduced almost all bases of both RNA strands, whereas other specific modifications must be placed only at certain positions within the siRNA strands [36] . For example, stability against nuclease degradation can be achieved via the introduction of a phosphorothioate (P=S) backbone linkage at the 3' end for exonuclease resistance and a 2' modifications (2'-O-methyl and 2'-fluoro) for endonuclease resistance [37][38][39][40] . In relation to maintaining RNAi silencing activity, exonuclease-stabilizing modifications are well tolerated.…”

Section: Increasing Stability Of Sirna Via Chemical Modificationsmentioning

confidence: 99%

Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

et al. 2010

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Access to the full text of the published version may require a subscription. Rights AbstractGene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate delivery systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.3 Introduction:

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Chemical modification of siRNAs to improve serum stability without loss of efficacy

Cited by 300 publications

References 31 publications

Noncanonical Synthetic RNAi Inducers

Noncanonical Synthetic RNAi Inducers

Structure - Functions Relations in Small Interfering RNAs

Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

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