Zata Pharmaceuticals, Inc.

The General Hospital Corporation

University of Massachusetts

The General Hospital Corporation Massachusetts

David R Tabatadze

Paul C Zamecnik

Ivan Yanachkov

Malay K Raychowdhury

Horacio F Cantiello

Alexei A Bogdanov

Valeriy Metelev

The invention relates to a method for the detection of natural or modified nucleic acids by their sequence specific hybridization with charge-modified oligonucleotide probes having charge-modifying groups attached to their backbones. The charge-modifying groups partially or fully neutralize the net negative charge of the backbone of the oligonucleotide probes or render them with a net positive charge. The charge-modified oligonucleotide probes may or may not be labeled, for example, with fluorescent, visible or near-infrared dye, with radioactive or stable isotopes, or with high specific affinity binding groups. The charge-modified oligonucleotide probes facilitate the separation of their hybrids with the targeted nucleic acids from the unhybridized probes or from any other components of the analyzed sample. They also allow for the modification and optimization of the properties of the hybrids with the targeted nucleic acids, such as melting temperature, chromatographic properties and off-target specificity.

Detection method for natural and modified small nucleic acids

Compositions and compounds of nucleoside phosphoramidites and modified oligonucleotides, each comprising one or more charge-neutralizing moieties according to the formula V The nucleoside phosphoramidites permit facile attachment of the neutralizing moieties on the backbones of the modified oligonucleotides. The modified oligonucleotides can be used as therapeutic agents (i.e., oligotherapeutics) for the treatment of cancer, autoimmune disorders, genetic diseases, infectious diseases, neurological diseases, inflammatory diseases, metabolic diseases and others.

Phosphoramidite synthones for the synthesis of self-neutralizing oligonucleotide compounds

Described herein are compositions and compounds having one or more aziridinyl groups, and methods of making the same. The compounds can also have one or more nitrogen atoms that each can be positively charged. The composition and compounds can inactivate one or more nucleic acid molecules (e.g. a DNA and/or a RNA from a pathogen) in a sample. The sample can comprise a blood or blood product (e.g., donated blood). The compositions and compounds can inactivate any nucleic acid present in a blood or blood product, thereby making the blood or blood product safe for use (e.g., in a transfusion).

Aziridinyl containing compounds and methods of inactivating nucleic acid molecules using the same

Compositions and compounds of nucleoside phosphoramidites and modified oligonucleotides, each comprising one or more charge-neutralizing moieties according to the formula V whereinrepresents the point of attachment to the nucleoside phosphoramidite or the oligonucleotide, optionally through a spacer group. The nucleoside phosphoramidites permit facile attachment of the neutralizing moieties on the backbones of the modified oligonucleotides. The modified oligonucleotides can be used as therapeutic agents (i.e., oligotherapeutics) for the treatment of cancer, autoimmune disorders, genetic diseases, infectious diseases, neurological diseases, inflammatory diseases, metabolic diseases and others.

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.

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Worcester, MA, United States of America

David R Tabatadze