Abstract: The present invention relates to methods of synthesis of stereodefined oligonucleotides wherein the protected 5?-hydroxy terminus of a nucleoside or oligonucleotide attached to a solid support is first unprotected, followed by coupling an oxazaphospholidine phosphoramidite monomer to the now deprotected 5?-hydroxy terminus, oxidizing the resultant phosphite triester intermediate with a sulfurizing reagent, and optionally washing the product. The method of synthesis of the present invention described above may be repeated to optionally elongate the stereodefined oligonucleotide being synthesized until the elongation cycle is intentionally terminated via deprotecting and cleavaging the resulting stereodefined oligonucleotide from the solid support. The oxazaphospholidine phosphoramidite monomer to be coupled in the present invention may optionally be chosen from Formula 1a and 1b.

Abstract: The present invention relates to a method for preparing stereodefined phosphorothioate oligonucleotides, especially locked stereodefined phosphorothioate oligonucleotides with a high yield, using pyridinium acidic salts as a coupling activator.

Abstract: The present invention relates to the field of stereodefined phosphorothioate oligonucleotides and to stereodefining nucleoside monomers comprising an amine containing chiral auxiliary group, and methods of orthogonally protecting the nitrogen of chiral auxiliaries during oligonucleotide synthesis, preventing post elongation chain cleavage, increasing yield and purity of stereodefined phosphorothioate oligonucleotides.

Abstract: The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to ATXN3 pre-mRNA sequences, which are capable of inhibiting the expression of ATXN3 protein. Inhibition of ATXN3 expression is beneficial for the treatment of spinocerebellar ataxia.

Abstract: The present invention relates to a novel process for preparing a compound of formula (III) and rhenium chelated MAG3 oligonucleotides.

Abstract: Stereodefined phosphorothioate oligonucleotides, related nucleoside monomers and methods of synthesis of both are described. The disclosed isobutyryl protected L-LNA-G monomers have following Formula 50 or 51 where R3 is independently CH2ODMTr or CH2OMMTr and R8, when present, is cyanoethyl. The monomers have improved solubility and stability characteristics, resulting in improved efficacy in oligonucleotide synthesis.

Abstract: The present invention relates to the synthesis of stereo-defined phosphorothioate oligonucleotides of formula I: Wherein Z, R1, R5, R6 and R9 are as defined herein. Phosphorothioate oligonucleotides are useful as therapeutics.

Abstract: The present invention relates to a method for preparing stereodefined phosphorothioate oligonucleotides, especially locked stereodefined phosphorothioate oligonucleotides with a high yield, using pyridinium acidic salts as a coupling activator.

Abstract: The present invention relates to the field of stereodefined phosphorothioate oligonucleotides and to stereodefining nucleoside monomers comprising an amine containing chiral auxiliary group, and methods of orthogonally protecting the nitrogen of chiral auxiliaries during oligonucleotide synthesis, preventing post elongation chain cleavage, increasing yield and purity of stereodefined phosphorothioate oligonucleotides.

Abstract: The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to ATXN3 pre-mRNA sequences, which are capable of inhibiting the expression of ATXN3 protein. Inhibition of ATXN3 expression is beneficial for the treatment of spinocerebellar ataxia.

Abstract: The present invention relates to methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides. The methods allow for the efficient identification of stereodefined variants with improved properties, such as enhanced in vitro or in vivo activity, enhanced efficacy, enhanced specific activity, reduced toxicity, altered biodistribution, enhanced cellular or tissue uptake, and/or enhanced target specificity (reduced off-target effects).

Abstract: The present invention relates to the field of stereodefined phosphorothioate oligonucleotidess and to nucleoside monomers and methods of synthesis thereof. Herein are disclosed acyl protected L-LNA-G monomers which have improved solubility and stability characteristics, and result in improved efficacy in oligonucleotide synthesis.

Abstract: The present invention relates to the field of stereodefined phosphorothioate oligonucleotides and to stereodefining nucleoside monomers and methods of synthesis of stereodefined oligonucleotides using said monomer. Herein are disclosed oligonucleotide enhanced synthesis methods where within a single elongation cycle there are repeated coupling and oxidation steps.

Abstract: The present invention relates to the field of stereodefmed phosphorothioate oligonucleotides and to stereodefining nucleoside monomers and methods of synthesis of stereodefmed oligonucleotides. Herein are disclosed solvent compositions which provide enhanced solubility and stability of stereodefining nucleoside monomers, and can be used to improve the coupling efficacy of such monomers in oligonucleotide synthesis.