Rheinische Friedrich-wilhelms-universitat Bonn

Rutgers, the State University of New Jersey

Memorial Sloan Kettering Cancer Center

University of Bonn

University of Iowa Research Foundation

The Rockefeller University

Coley Pharmaceutical Gmbh

Coley Pharmaceutical Group, Inc.

Other

Alnylam Pharmaceuticals, Inc.

Rheinische Friedrich-wilhelms-universitaet Bonn

Rheinische Friedrich-Wilhelms-Universität

Hartmann, Gunther, Prof. Dr.

Gunther Hartmann

Winfried Barchet

Thomas Tuschl

Roger A Jones

Dinshaw J Patel

Veit Hornung

Manuel Ascano, Jr

Thomas Zillinger

Pu Gao

Barbara L Gaffney

Yang Wu

Yizhou Liu

Arthur Mertz Krieg

Martin Schlee

Robert L Bratzler

Antonin De Fougerolles

Liang Deng

Weiyi Wang

George J Weiner

Stefan Endres

Vera Wimmenauer

Christoph Coch

Juliane Dassler-Plenker

Roger Jones

Manuel Ascano

The present invention pertains to extracellular vesicles (exosomes) that are produced by culturing tumor cells in the presence of various ligands or activators of innate immunity receptors and subsequently isolating and purifying the vesicles in the culture supernatant. The invention provides also pharmaceutical compositions comprising the inventive exosomes. The exosomes of the invention are provided as medicaments for example in the treatment of cancer diseases.

Cell derived extracellular vesicles for the treatment of diseases

The present disclosure provides, among other things, compounds comprising cyclic dinucleotides containing a 2',5' linkage useful in the design of research tools, as research tools, and as therapeutic modalities such as enzyme modulators.

Compositions and methods for altering second messenger signaling

The invention relates to compositions, methods, kits, and assays related to the use and/or exploitation of isomers of cGAMP as well as the structure of the enzyme cGAS.

Oligonucleotides bearing free, uncapped 5' phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1&#x3b2; production. Bacterial RNA also induces type I IFN production. 5&#x2032; phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1&#x3b2; production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5&#x2032; triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1&#x3b2; production, in a target cell-specific manner.

Structure and use of 5' phosphate oligonucleotides

The present invention provides an oligonucleotide which is capable of activating RIG-I and inducing an anti-viral, in particular, an IFN, response in cells expressing RIG-I. The present invention further provides an oligonucleotide which is capable of activating RIG-I and which has target gene-silencing activity. The oligonucleotide of the present invention has a double-stranded section of at least 19, preferably at least 21 bp, at least one 5' triphosphate, and at least one blunt end which bears a 5&#x2032; triphosphate. The present invention further provides the use said oligonucleotide for inducing an anti-viral, in particular, an IFN, response in vitro and in vivo. The present invention additionally provides the use of said oligonucleotide for preventing and/or treating diseases or conditions such as infections, tumors/cancers, and immune disorders.

5' triphosphate oligonucleotide with blunt end and uses thereof

The present invention provides STING crystals. The present invention also provides STING modulators that interact with sites present in and/or defined by such crystals. The present invention also provides methods of making and using such crystals and modulators. Other aspects and/or features of the present invention will be apparent to those skilled in the art, reading the present specification.

STING crystals and modulators

The present invention provides a TLR7 ligand and its use in therapeutic applications. Specifically, the present application provides a RNA oligonucleotide comprising a G:U wobble base pair in the context of a fully double-stranded structure and its use in treating disease such as viral infections, immune disorders and cancer.

TLR7 ligand and uses thereof

The present disclosure provides, among other things, novel cyclic-GMP-AMP (cGAMP) analogs, mimics, mimetics and variants, and compositions and kits thereof; methods of using the compounds as described herein for treating cancer, and immune disease, disorders, or conditions; methods of using the compounds as described herein for modulating cGAS and STING; and methods of designing or characterizing a cGAS modulator.

The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IL-12-inducing activity to a single-stranded RNA oligonucleotide. The present invention also provides single-stranded RNA oligonucleotides, including antisense RNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Compositions and methods for immunostimulatory RNA oligonucleotides

The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-&#x3b1;-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Method for determining immunostimulatory activity of RNA oligonucleotides

This invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

Method of stimulating an immune response and inhibiting expression of a gene using an oligonucleotide

Growing community of inventors

Bonn, Germany

Gunther Hartmann