Hybridon, Inc.

Ivan Habus

Sudhir Agrawal

Dong Yu

Radhakrishnan P Iyer

Theresa Devlin

Qiuyan Zhao

Ekambar R Kandimalla

Nan-Hui Ho

The invention provides synthons containing a novel carbamate internucleoside linkage, methods for using such synthons to make oligonucleotides containing such novel carbamate linkages, and oligonucleotides containing such novel carbamate linkages.

Building blocks with carbamate internucleoside linkages and oligonucleotides derived therefrom

The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.

Base protecting groups and synthons for oligonucleotide synthesis

Base protecting groups and rapid process for oligonucleotide synthesis

The invention provides new primary phosphoramidate internucleoside linkages that are less sterically constrained than existing phosphoramidate linkages, as well as oligonucleotides containing such linkages and processes for making and methods for using such oligonucleotides.

Primary phosphoramidate internucleoside linkages and oligonucleotides

The invention provides new reagents and an improved process for synthesizing oligonucleotides that contain methylphosphonate internucleoside linkages. The reagents and process utilize a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups.

Synthesis of oligonucleotides containing alkylphosphonate

The invention provides oligonucleotides containing methyl phosphotriester linkages and processes for making and methods for using such oligonucleotides.

Process for making oligonucleotides containing o- and s-

The present invention provides novel compounds and methods for purifying oligonucleotides. The compounds according to the invention are multimeric oligonucleotides comprising a multimerization domain for inducing multimeric oligonucleotide aggregation, a hybridization domain that is complementary to a target oligonucleotide whose isolation is desired, and a linker domain connecting the multimerization domain and the hybridization domain. Other compounds of the invention comprise dendrimers having oligonucleotides with hybridization domains linked thereto. The methods of the invention comprise contacting the compounds of the invention with a solution containing a target oligonucleotide whose purification is desired. The target oligonucleotide hybridizes to the hybridization domain of the inventive compounds, thereby forming an aggregate. Synthetic failure sequences (N-1, N-2, etc.) and other oligonucleotides not complementary to the hybridization domain do not hybridize with the hybridization domain of the compounds and remain free in solution. Conventional size exclusion chromatography or small pore filter membranes are then used to separate the aggregate (and hence target oligonucleotide) from the other oligonucleotides. The aggregate is denatured and the target oligonucleotide separated once again by size exclusion chromatography or with a small pore filter membrane.

Affinity-based purification of oligonucleotides using soluble multimeric

Disclosed is a composition including an oligonucleotide complexed with a cyclodextrin. The oligonucleotide may be noncovalently associated with the cyclodextrin. Alternatively, the oligonucleotide may be covalently complexed with adamantane which is noncovalently associated with the cyclodextrin. Also disclosed are methods of enhancing the cellular uptake and intracellular concentration of oligonucleotides, methods of increasing the solubility of an oligonucleotide in a cell, and methods of treating a cell for viral infection or to prevent viral infection.

Cyclodextrin cellular delivery system for oligonucleotides

The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotide under more mild conditions than existing methods. The invention further provides a nucleoside base protective group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protective groups, as well as nucleoside synthons having such base protective groups.

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Shrewsbury, MA, United States of America

Ivan Habus