University of Texas System

Beth Israel Deaconess Medical Center, Inc.

Children's Medical Center Corporation

Georg-august-universitaet Goettingen Stiftung Oeffentlichen Rechts, Universitaetsmedizin

Georg-august-universität Göttingen Stiftung Öffentichen Rechts, Universitätsmadizin

Raghu Kalluri

Sónia Melo

Elizabeth J Shpall

Katy Rezvani

Elisabeth Zeisberg

Sushrut Kamerkar

Valerie Lebleu

Mayela Mendt

Désiree Tampe

Michael Zeisberg

Gerhard Anton Mueller

Judah M Folkman

Bjoern Tampe

Xu Xingbo

Björn Tampe

Sonia Melo

The present invention provides methods of diagnosing and prognosing disease by analyzing the methylation status of exosomal DNA. In particular, exosomal DNA, in particular exosomal DNA isolated from exosomes that originated from a diseased cell, is analyzed for either a global methylation fingerprint or for a particular methylation status at one or more genomic loci, thereby providing information regarding the disease-state of the originated cell.

Identification of epigenetic alterations in DNA isolated from exosomes

The present disclosure is directed to novel therapeutic approaches for the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of an organ. Specifically disclosed are agents for use in increasing homodimer-formation of ARNT in an organ in the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of said organ, as further defined in the claims. In embodiments, said agent may be (i) an inhibitor of protein phosphatase 2A (PP2A) activity, (ii) an inhibitor of the transcriptional repressor complex FKBP12/YY1, or (iii) an expression construct, which is capable of over-expressing ARNT in said organ, as well as combinations of (i), (ii), and/or (iii).

Prevention or treatment of chronic organ injury

Provided herein are methods of manufacturing clinical grade exosomes derived from mesenchymal stem cells (MSCs). Further provided are methods of loading the exosomes with therapeutic agents, such as siRNA. Also provided herein are methods of treating diseases by administering the clinical grade exosome.

Methods for production of MSC-derived exosomes

Methods for diagnosis and treatment of cancers by use of exosomes comprising miRNAs and precursors thereof. For example, in some aspects, a cancer may be diagnosed or evaluated by determining the miRNA content of exosomes in a sample from a subject or by detecting miRNA processing in exosomes.

miRNA biogenesis in exosomes for diagnosis and therapy

Provided herein are methods of manufacturing clinical grade exosomes derived from mesenchymal stem cells (MSCs). Further provided are methods of loading the exosomes with therapeutic agents, such as siRNA. Also provided herein are methods of treating diseases by administering the clinical grade exosomes.

Provided is a method of preventing, treating or delaying progression of a disease involving aberrant fibroblast proliferation. The method involves using a compound that reduces the level of tyrosine phosphatase activity effected by the protein EYA1A in the parenchymal organ, a nucleic acid ligase IV inhibitor, or an antisense oligonucleotide against the p53-binding protein 1 (53BP1).

Treatment of aberrant fibroblast proliferation

The present invention provides lipid-based nanoparticles (e.g., liposomes or exosomes) having CD47 on their surface and comprising a therapeutic agent (e.g., a therapeutic protein, an antibody, an inhibitory RNA, and/or a small molecule drug). Furthermore, the present invention provides for use of such lipid-based nanoparticles in therapy.

Use of exosomes for the treatment of disease

The present invention provides that exosomes from human body fluid samples contain double stranded genomic DNA that spans all chromosomes and may be used to determine the mutation status of genes of interest in diseases, such as cancer. Furthermore, the present invention provides the use of exosomes to produce therapeutic proteins and for their use in therapy as well as the detection of cancer cell-derived exosomes to diagnose cancer and monitor therapeutic response.

Analysis of genomic DNA, RNA, and proteins in exosomes for diagnosis and theranosis

The invention features methods for diagnosing and treating pregnancy related complications. The invention also features methods for identifying compounds useful for treating pregnancy related complications.

Hypoxia related genes and proteins for the treatment and diagnosis of pregnancy related complications

Methods and compositions for treating and/or preventing a pregnancy related disease or disorder are provided. The methods involve administration of 2-methoxyestradiol, or an analog thereof, to a subject. Also provided are methods for diagnosing or predicting a pregnancy related disease or disorder. The methods involve detection of 2-methoxyestradiol, or a precursor or metabolite thereof.

Growing community of inventors

Houston, TX, United States of America

Raghu Kalluri