The University of Texas System

Purdue Research Foundation

Am Biotechnologies, Inc.

Mei Technologies, Inc.

David G Gorenstein

Bruce A Luxon

Allan R Brasier

James F Leary

Johnnie Engelhardt

Norbert Herzog

Xianbin Yang

David J King

Daniel A Ventura

Ross Durland

Nassar Farschtschi

Miguel-Angel Elizondo-Riojas

Takemi Tanaka

Weiguo He

Anoma Somasunderam

Aman Mann

David E Volk

Judy Aronson

Provided herein are methods for a novel bead-based next-generation 'X-aptamer' selection scheme that extends aptamer technology to include X-modified bases, thus resulting in X-aptamers, at any position along the sequence because the aptamers are chemically synthesized via a split-pool scheme on individual beads. Also provides are application to a wide range of commonly used DNA modifications, including, but not limited to, monothioate and dithioate backbone substitutions. This new class of aptamer allows chemical modifications introduced to any of the bases in the aptamer sequence as well as the phosphate backbones and can be extended to other carbohydrate-based systems.

Methods of X-aptamer generation and compositions thereof

The present invention includes composition and methods for making and using a combinatorial library to identify modified thioaptamers that bind to, and affect the immune response of a host animal, transcription factors such as IL-6, NF-&#x3ba;B, AP-1 and the like. Composition and methods are also provided for the treatment of viral infections, as well as, vaccines and vaccine adjuvants are provided that modify host immune responses.

Structure based and combinatorially selected oligonucleoside phosphorothioate and phosphorodithioate aptamer targeting AP-1 transcription factors

An isolated nucleic acid molecule that selectively binds to an E-selectin protein comprises a contiguous 29-30 nucleotide sequence that includes at least one monothiophosphate or a dithiophosphate modified nucleotide. Also disclosed are methods of inhibiting an E-selectin mediated interaction with a natural E-selectin ligand, and methods of targeting an imaging agent or therapeutic agent to a target tissue bearing E-selectin.

Aptamer-containing compositions and methods for targeting E-selectin

Apparatus and methods are described for split synthesis combinatorial chemistry that provides candidate libraries where an even distribution of theoretical products is obtainable through even mixing during the pooling step, followed by controlled redistribution of the mixed pooled products from the prior addition step into separate synthesis columns, one for each different specie of subunit to be added.

Process and apparatus for combinatorial synthesis

The present invention includes composition and methods for making and using a combinatorial library having two or more beads, wherein attached to each bead is a unique nucleic acid aptamer that have disposed thereon a unique sequence. The library aptamers may be attached covalently to the one or more beads, which may be polystyrene beads. The aptamers may include phosphorothioate, phosphorodithioate and/or methylphosphonate linkages and may be single or double stranded DNA, RNA or even PNAs.

Bead bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries

A random combinatorial selection method is disclosed for the construction of oligonucleotide aptamers in which nuclease resistance is conferred by the inclusion of modified nucleotides. The modified nucleotides are incorporated during PCR amplification to form achiral modified oligonucleotides. Thio-substituted aptamers are provided that bind tightly to the nuclear factor for human IL6 (NF-IL6).

Combinatorial selection of oligonucleotide aptamers

This invention generally relates the generation of aptamers and to the use of aptamers as diagnostic and therapeutic agents. More particularly, the present invention relates to methods using combinatorial chemistry to prepare aptamers having controlled thiophosphate replacement in the phosphate backbone for improved binding efficiencies to a target and to RNA and/or DNA products having novel nucleotide sequences and enhanced target binding efficacies.

Thio-modified aptamer synthetic methods and compositions

A method for synthesis of oligonucleotide analogs having dithiophosphate internucleosidic linkages is described. Monohalohydrocarbylthiophosphoramidites are utilized to prepare nucleoside thiophosphoramidite intermediates which are activated for nucleoside coupling with tetrazole catalysts. Sulfur oxidation and dehydrocarbylation of the coupled thiophosphite intermediates provide oligonucleotide analogs having achiral dithiophosphate internucleosidic linkages.

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Houston, TX, United States of America

David G Gorenstein