Abstract: The present invention relates to pyrazolotriazolyl nucleoside analogues, oligonucleotide comprising them, and uses thereof. Further the invention relates to a method for reducing gene expression in a cell comprising transfecting the cell with such an oligonucleotide.

Abstract: Disclosed herein are double-stranded RNA nucleic acid molecules, which include at least one pyrazolotriazine nucleotide analog and have been modified to exhibit one of the following, increased on-target activity, increased target specificity, enhanced nuclease stability, reduced off target activity and/or reduced immunogenicity when compared to an unmodified or similarly modified dsRNA; pharmaceutical compositions comprising such molecules and methods of use thereof in therapy.

Abstract: The present invention relates to pyrazolotriazolyl nucleoside analogs, such as oligonucleotide comprising them, and uses in treatment of hepatitis C virus infections. Further the invention relates to a method for reducing gene expression in a cell comprising transfecting the cell with such an oligonucleotide.

Abstract: Disclosed herein are novel compounds having the general formula (I): Q-L-A1??(I) wherein Q is a Q10 moiety, such as ubiquinone; L, which is optionally included, is a linker selected from the group consisting of polyesters, polyethers, polyamines, polyamides, peptides, carbohydrates, lipids, C3-12 alkyl straight chain based linkers, polyethylene glycols and other polymeric compounds; and A1 is a nucleotide moiety. Disclosed are also pharmaceutical compositions comprising such compounds or pharmaceutically acceptable salts thereof. Further disclosed is the use of such compounds in the treatment of cancer and/or a cancer related medical condition.

Abstract: Disclosed herein are double-stranded RNA nucleic acid molecules, which include at least one pyrazolotriazine nucleotide analogue and have been modified to exhibit one of the following, increased on-target activity, increased target specificity, enhanced nuclease stability, reduced off target activity and/or reduced immunogenicity when compared to an unmodified or similarly modified dsRNA; pharmaceutical compositions comprising such molecules and methods of use thereof in therapy.

Abstract: The present invention relates to pyrazolotriazolyl nucleoside analogues, oligonucleotide comprising them, and uses thereof. Further the invention relates to a method for reducing gene expression in a cell comprising transfecting the cell with such an oligonucleotide. It has been found, in accordance with the present invention, that certain pyrazolotriazolyl-based nucleoside analogues such as 8-[3?-(2-cyanoethyl)-(N,Ndiisopropyl)]-phosphoramidite-(2?-deoxy-5?-dimethoxytrity 1-13-D-ribofuranozyl)-4-{N-benzoylamino)-pyrazolo[1,5a]-1,3,5-triazine, can be incorporated into oligonucleotides, substituting natural purine nucleosides and imparting acid stability and nuclease stability to the oligonucleotide. Furthermore, oligonucleotides comprising one or more such nucleoside analogues are capable of hybridizing with oligonucleotides having complementary sequences thereto in which no such analogues are incorporated.