RNA Interference in Mammalia Cells by RNA-3’-PNA Chimeras

Potenza, Nicoletta; Moggio, Loredana; Milano, Giovanna; Salvatore, Vincenzo; Blasio, Benedetto Di; Russo, Aniello; Messere, Anna

doi:10.3390/ijms9030299

Cited by 38 publications

(28 citation statements)

References 46 publications

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“…The modified siRNAs retained RNAi activity and achieved inhibition at concentrations as low as 0.1 nm, while maintaining activity over increasing incubation times when compared to the native siRNA. [89] 5. Other Applications of Modified Oligonucleotides…”

Section: Rnaimentioning

confidence: 99%

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

2009

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Although known for more than a century, bromine trifluoride is not a common reagent in day to day research work in organic chemistry. Its tendency to react exothermically with solvents containing Lewis base elements such as water, acetone or ethers distanced it from the mind of many. Still, under the proper conditions, it can perform quite a few selective reactions which are difficult to achieve by other reagents. We discuss in this review reactions which have been published in the last 30 years. They consist of fluorinating heteroatoms, substituting carbon‐halogen bonds with carbon‐fluorine bonds, syntheses of anesthetics, construction of the trifluoromethyl (CF3) and the difluoromethylene (CF2) groups, aromatic brominations and more.

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Section: Rnaimentioning

confidence: 99%

Chemical Modification of Oligonucleotides for Therapeutic, Bioanalytical and other Applications

2009

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“…Messere and co-workers have shown that a siRNA-PNA chimera can be used for efficient silencing along with improved serum stability and persistent activity. [87] The PNAs were conjugated to thymine dimers in the 3' overhang of one or both strands of the siRNA. The siRNAs having PNA monomers at the passenger strand overhangs showed efficient gene silencing and also showed persistent silencing activity relative to other siRNAs tested.…”

Section: Challenges Involved In Sirna Therapeutics and Opportunities mentioning

confidence: 99%

Exploring Chemical Modifications for siRNA Therapeutics: A Structural and Functional Outlook

2010

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RNA interference (RNAi) is a post-transcriptional gene silencing mechanism induced by small interfering RNAs (siRNAs) and micro-RNAs (miRNAs), and has proved to be one of the most important scientific discoveries made in the last century. The robustness of RNAi has opened up new avenues in the development of siRNAs as therapeutic agents against various diseases including cancer and HIV. However, there had remained a lack of a clear mechanistic understanding of messenger RNA (mRNA) cleavage mediated by Argonaute2 of the RNA-induced silencing complex (RISC), due to inadequate structural data. The X-ray crystal structures of the Argonaute (Ago)-DNA-RNA complexes reported recently have proven to be a breakthrough in this field, and the structural details can provide guidelines for the design of the next generation of siRNA therapeutics. To harness siRNAs as therapeutic agents, the prudent use of various chemical modifications is warranted to enhance nuclease resistance, prevent immune activation, decrease off-target effects, and to improve pharmacokinetic and pharmacodynamic properties. The focus of this review is to interpret the tolerance of various chemical modifications employed in siRNAs toward RNAi by taking into account the crystal structures and biochemical studies of Ago-RNA complexes. Moreover, the challenges and recent progress in imparting druglike properties to siRNAs along with their delivery strategies are discussed.

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“…The increase of the siRNA silencing activity was observed when modifications were introduced in the sense strand. In the other cases the activity of PNA-containing siRNA was comparable with activity of the unmodified siRNA [110]. Due to the functional inequivalence of siRNA strands the modifications in the sense strand a better tolerated than modifications in the antisense strand.…”

Section: Structural Modifications Of the Furanose Ringmentioning

confidence: 89%