Worcester Foundation for Experimental Biology

The General Hospital Corporation

Other

Worcester Foundation for Biomedical Research

University of Massachusetts

Mount Sinai School of Medicine

Hybridon, Inc.

Prp, Inc.

The General Hospital Corporation Massachusetts

Paul C Zamecnik

Sudhir Agrawal

Eliezer Rapaport

David R Tabatadze

Thoru Pederson

Sandra Mayrand

Malay K Raychowdhury

Horacio F Cantiello

Peter M Palese

Josef M Leiter

David R Elmaleh

John W Babich

Alexei A Bogdanov

Valeri Metelev

John Goodchild

Robert H Barker, Jr

Byung K Kim

Asya Levina

Valeriy Metelev

Compositions and methods of treatments of cells are provided for altering the phenotype of a cell by administering an oligonucleotide complex to the cell, the complex having two strands and chemical modifications.

Oligonucleotide complex compositions and methods of use as gene alteration tools

Described are phosphoramidite nucleoside analog monomers, precursors thereof, and oligonucleotides including one or more of the monomers. The monomers can be used during automated synthesis of oligonucleotide derivatives, and allow for incorporation of one or several reporter groups, organic molecules, bio-molecules, small molecules or other chemical groups at the internucleoside phosphotriesters. Oligonucleotides including the monomers have a number of uses in therapeutic, diagnostic, and research applications.

Phosphoramidite nucleoside analogs

The present invention provides methods of resensitizing an anti-drug-resistant infectious agent to a drug. Also disclosed are synthetic oligonucleotides having a nucleotide sequence complementary to a region of pfmdr1 nucleic acid, and methods of down-regulating the expression of pfmdr nucleic acid using such oligonucleotides.

Oligonucleotide mediated reversal of drug resistance

The invention discloses methods and materials for the utilization of chemically modified oligonucleotides in the treatment of drug-resistant bacterial infections including drug-resistant tuberculosis.

Oligonucleotides active against drug-resistant bacteria

The invention provides cardiovascular imaging agents comprising a radionuclide in association with a nucleotide polyphosphate targeting molecule. Methods for using the cardiovascular imaging agents and kits containing the cardiovascular imaging agents or components suitable for production of the cardiovascular imaging agents are also provided.

Cardiovascular and thrombus imaging agents, methods and kits

Compositions of antisense oligonucleotides conjugated to peptides of a plurality of N-methylpyrrolecarboxamides linked by peptide bonds is provided. The compositions form stable hybridization complexes with DNA and can be used for any purpose which involves hybridizing an oligonucleotide to a DNA molecule, such as in antisense procedures. A method for enhancing oligonucleotide binding to a target is also provided. The method involves the step of hybridizing the target DNA with an oligonucleotide-peptide composition.

Conjugates of minor groove DNA binders with antisense oligonucleotides

A novel composition, P.sup.1, P.sup.4 -dithio-P.sup.2, P.sup.3 -monochloromethylene 5', 5''-diadenosine P.sup.1, P.sup.4 -tetraphosphate, is disclosed. The composition is useful as a therapeutic agent for prevention of thrombosis and for modulating a thrombolytic effect in a mammal.

P.sup.1, P.sup.4 -dithio-P.sup.2 -P.sup.3 -monochloromethylene 5',

A method of inhibiting influenza virus replication through the activity of natural (unmodified) or modified oligonucleotides (oligodeoxynucleotides or oligoribonucleotides) which hybridize to a selected region of the influenza virus RNA and interfere with its ability to serve as a template for synthesis of encoded products. Oligonucleotides (unmodified or modified) which have antiviral activity against influenza virus as a result of their ability to hybridze to a selected region of influenza virus RNA and inhibit its ability to serve as a template for synthesis of encoded products, as well as compositions which include the oligonucleotides.

Influenza virus replication inhibiting oligonucleotide analogues and

A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.

Method of site-specific alteration of RNA and production of encoded

The invention provides methods and materials for antisense oligonucleotide therapy against active pathogenic infection by drug resistant or drug sensitive pathogens, including Plasmodium falciparum.

Antiparasitic oligonucleotides active against drug resistant malaria

A method of purifying full length synthetic target oligonucleotides from a mixture of oligonucleotides, particularly from a mixture containing truncated or failed sequences. The method involves attaching a short nucleotide sequence complementary to the 5' end of a target oligonucleotide to a solid support. The complementary between the most 5' nucleotides of the target oligonucleotide and the bound oligonucleotide results in hybridization which serves to retain the target oligonucleotide. Truncated or failed sequences lacking 5' sequences complementary to the attached oligonucleotide, fail to hybridize and therefore are not retained. The method makes it possible to purify gram quantities of synthetic deoxyribonucleic acids or ribonucleic acids and sequences which have modifications, such as on the phosphate backbone. The support-bound nucleotide sequences are stable under conditions of purification and therefore can be reused.

Method of separating oligonucleotides from a mixture

A method of purifying full length synthetic target oligonucleotides from a mixture of oligonucleotides, particularly from a mixture containing truncated or failed sequences is disclosed. The method involves attaching a short nucleotide sequence complementary to the 5' end of a target oligonucleotide to a solid support. The complementarity between the most 5' nucleotides of the target oligonucleotide and the bound oligonucleotide results in hybridization which serves to retain the target oligonucleotide. Truncated or failed sequences lacking 5' sequences complementary to the attached oligonucleotide, fail to hybridize and therefore are not retained. The method makes it possible to purify gram quantities of synthetic deoxyribonucleic acids or ribonucleic acids and sequences which have modifications, such as on the phosphate backbone. The support-bound nucleotide sequences are stable under conditions of purification and therefore can be reused.

Growing community of inventors

Shrewsbury, MA, United States of America

Paul C Zamecnik