Use of exosomes for the treatment of disease

a technology of exosomes and disease, applied in the field of exosomes, can solve problems such as antibody disruption

Inactive Publication Date: 2018-06-28
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0027]As used herein the specification, “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising,” the words “a” or “an” may mean one or more than one.
[0028]The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” As used herein “another” may mean at least a second or more.

Problems solved by technology

In some cases, the antibody disrupts a protein-protein interaction.

Method used

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  • Use of exosomes for the treatment of disease
  • Use of exosomes for the treatment of disease
  • Use of exosomes for the treatment of disease

Examples

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Effect test

example 1

r Properties of Inhibitory RNA-Containing Exosomes

[0213]siRNA and shRNA constructs were designed to specifically target KrasG12D. The siRNA sequence (GUUGGAGCUGAUGGCGUAGTT; SEQ ID NO: 1) reflects a G to A nucleotide deviation from the wild-type Kras gene sequence (underlined and bold) so as to specifically target the Glycine to Aspartate amino acid substitution in the KrasG12D mutation found in cell lines and animal models, and a TT nucleotide overhang (underlined) to promote silencing efficiency (Rejiba et al., 2007; Ma et al., 2004; Du et al., 2005). The central position of the nucleotide deviant in this KrasG12D siRNA enhances its specificity against the wild-type mRNA sequence (Du et al., 2005). The shRNA sequence (SEQ ID NO: 2) was designed to contain the specific G to A nucleotide deviation in the seed sequence to promote the specific targeting of KrasG12D mRNA. The siRNA oligonucleotides for KrasG12D were also labeled with an Alexa Fluor® 647 fluorophore to track their delive...

example 2

ents Uptake of Exosomes by Circulating Monocytes

[0217]Circulating monocytes were found to engulf liposomes (100 nm; purchased from Encapsula Nanosciences) but not exosomes (FIGS. 8A-8B). Exosomes isolated from BJ fibroblasts were found to comprise CD47 on their surface (FIGS. 9A and 9C) while liposomes were determined to lack CD47 on their surface (FIG. 9B). Treatment of exosomes with an anti-CD47 antibody was found to stimulate the uptake of exosomes by circulating monocytes in vivo (FIG. 10).

[0218]All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. Mor...

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Abstract

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.

Description

[0001]The present application claims the priority benefit of U.S. provisional application No. 62 / 173,838, filed Jun. 10, 2015, the entire contents of which is incorporated herein by reference.BACKGROUND OF THE INVENTION1. Field of the Invention[0002]The present invention relates generally to the field of medicine and oncology. More particularly, it concerns the use of exosomes in methods of treatment.2. Description of Related Art[0003]Exosomes are small (40-150 nm) membrane vesicles with a lipid bilayer of endosomal origin that are released by all cells of the body (Kowal et al., 2014; El-Andaloussi et al., 2013; Thery et al., 2002). Exosomes contain proteins, lipids, mRNA, microRNAs (miRNAs) and genomic DNA (Valadi et al., 2007; Peinado et al., 2012; Luga et al., 2012; Kahlert et al., 2014). Unlike liposomes and other synthetic drug nanoparticle carriers, exosomes contain many transmembrane and membrane anchored proteins that likely enhance endocytosis and / or direct fusion with the...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/127A61K9/00A61K45/06A61P35/00C12N15/113
CPCA61K9/1271A61K9/0019A61K45/06A61P35/00C12N15/1135C12N2310/14A61K31/7088A61K47/46C12N15/113A61K9/127A61K9/5068C12N15/88A23L29/20A23L29/212A23L29/231A23L29/238A23L29/25A23L29/256A23L29/262A23L29/269A23L33/185A23L33/40A61K39/395A61K47/42A61K48/00A61K49/0084A23L23/10A23L25/10A23L27/60A23L9/10A23C19/0904A23V2002/00
Inventor KALLURI, RAGHUMELO, SONIA
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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