Alnylam Pharmaceuticals, Inc.

Alexander V Kelin

Muthiah Manoharan

Kallanthottathil G Rajeev

Shigeo Matsuda

Jayaprakash K Nair

Pachamuthu Kandasamy

Muthusamy Jayaraman

Narayanannair K Jayaprakash

Sudhakar Rao Takkellapati

Rajeev G Kallanthottathil

The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.

Oligonucleotide-ligand conjugates and process for their preparation

The present invention relates to ligand conjugates of iRNA agents (such as siRNA) of the formula 

This disclosure relates to an improved process for the preparation of carbohydrate conjugates. The disclosure also relates to carbohydrate conjugated iRNA agents comprising these carbohydrate conjugates, which have improved purity and are advantageous for the in vivo delivery of the iRNA agents.

Carbohydrate conjugated RNA agents and process for their preparation

The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least one nucleoside of formula (2): Another aspect of the invention relates to a method of inhibiting the expression of a gene in cell, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

Nucleic acid chemical modifications

The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least one nucleoside of formula (2): Another aspect of the invention relates to a method of inhibiting the expression of a gene in cell, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. 

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Cambridge, MA, United States of America

Alexander V Kelin