New York University

Massachusetts Institute of Technology

Evgeny A Nudler

Ilya Shamovsky

Ruslan R Rafikov

Bhubaneswar Mishra

Stephen J Lippard

Andrei Nedospasov

Audrei Nedospasov

Bibhusita Pani

Ruslan Rafikova

Olga Rafikova

Justin Lee

Lindsey E McQuade

A method for detecting rare genomic variants in a population of cells is disclosed. The method can detect de novo mutations in bacteria and analyze the impact of various physiological conditions on mutation rate, even though such effects would be too subtle to detect using other methods. The method can be used for detection of low-frequency subpopulations in the microbiome or in cancer.

Sequencing methods and kits

The invention provides siRNA molecules, combinations of such siRNA molecules, and locked nucleic acid (LNA) antisense oligonucleotides, which target Heat Shock RNA (HSR1) and effectively inhibit stress response in a cell, as well as the use of such siRNA molecules and LNA antisense oligonucleotides for inhibiting inflammatory reactions, inhibiting HIV transcription, and treatment of various diseases, including autoimmune diseases and cancer.

SiRNA targeting HSR1

The present invention is directed to molecules that inhibit expression or a function of a eukaryotic Heat Shock RNA (HSR1) and their use for inhibiting a stress response or stress tolerance in a cell.

Inhibitors of heat shock RNA

This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH; SEQ ID NOS: 1 and 15) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia/reperfusion (I/R) injury and other disorders.

Short peptides useful for treatment of ischemia/reperfusion injury and other tissue damage conditions associated with nitric oxide and its reactive species

The invention relates in part to compounds that act as highly nitric oxide (NO)-specific turn-on fluorescent probes. The present invention also relates to the use of these fluorescein-based sensors to screen selectively for inhibitors of bacterial nitric oxide synthase (bNOS). Compounds of the present invention readily detect nitric oxide produced in vivo. Therefore they can be used in an assay that measures NO production by bNOS. Using a sensor of the invention one can screen libraries of small molecules for inhibitors of bNOS.

Inhibitors of bacterial nitric oxide synthase, and related screening methods

This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH; SEQ ID NOS: 1 and 15) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia/reperfusion (I/R) injury of various tissues (e.g., I/R injury of heart muscle associated with heart attack or cardiac surgery, I/R injury of brain tissue associated with stroke, I/R injury of liver tissue, skeletal muscles, etc.), septic shock, anaphylactic shock, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's diseases), neuronal injury, atherosclerosis, diabetes, multiple sclerosis, autoimmune uveitis, pulmonary fibrosis, oobliterative bronchiolitis, bronchopulmonary dysplasia (BPD), amyotrophic lateral sclerosis (ALS), sepsis, inflammatory bowel disease, arthritis, allograft rejection, autoimmune myocarditis, myocardial inflammation, pulmonary granulomatous inflammation, influenza- or HSV-induced pneumonia, chronic cerebral vasospasm, allergic encephalomyelitis, central nervous system (CNS) inflammation,gastritis, necrotizing entrerocolitis, celliac disease, peritonitis, early prosthesis failure, inclusion body myositis, preeclamptic pregnancies, skin lesions with anaphylactoid purpura, nephrosclerosis, ileitis, leishmaniasis, cancer, and related disorders.

The present invention provides a novel RNA, designated herein as the 'HSR1' (Heat Shock RNA), constitutively active HSR1 fragments, and the use of HSR1 and constitutively active HSR1 fragments for generation of novel therapeutics for the treatment of various diseases in animals and for generation of stress-resistant plants.

Constitutively active fragments of eukaryotic heat shock RNA

Biomacromolecules such as proteins are inactivated by hydrophobic ANSA derivatives of the formula: wherein Rand Rare hydrophobic or affinity groups and Ris selected from the group consisting of aminoacyl groups and peptidyl groups upon nitrosation. ANSA derivatives can be designed to selectively kill tumor cells and various pathogens, including bacteria, viruses, and fungi.

Nitrosation-inducible inhibitors biological macromolecules

The present invention provides a novel RNA, designated herein as the 'HSR1' (Heat Shock RNA), and its use together with translation elongation factor eEF1A in activation of heat shock transcription factor HSF. The invention further provides the use of HSR1 for generation of novel therapeutics for the treatment of cancer, inflammation, ischemia, neurodegeneration, age-related diseases, HIV infection, deafness, and related disorders.

Heat shock RNA

Perfluorocarbons are used to control nitric oxide metabolism, either to inhibit nitric oxide activity or to potentiate the effects of nitric oxide. Perfluorocarbons can be used, for example, to treat hypotension and vasoplegia in septic shock, to protect against myocardial ischemia-reperfusion injury, to treat hypertension, and to provide antiplatelet effects.

Growing community of inventors

New York, NY, United States of America

Evgeny A Nudler