Exosome packaging and targeted autophagy
a technology of autophagy and exosomes, applied in the direction of specific cell targeting fusions, peptide sources, antibody medical ingredients, etc., can solve the problems of impeded neurodegenerative disease treatment, difficult delivery of protein-containing active agents such as antibodies and antibody-like proteins to certain tissues/cells such as those of the brain, etc., and achieve the effect of low or reducing the level of atg7
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example 1
ociates the V1V0-ATPase to Promote Exosome Production and Tumor Metastasis Independent of Canonical Macroautophagy
[0230]Autophagy and Autophagy-related genes (Atg) have been attributed prominent roles in tumorigenesis, tumor growth and metastasis. Extracellular vesicles called exosomes are also implicated in cancer metastasis. This Example demonstrates that exosome production is strongly reduced in cells lacking Atg5 and Atg16L1, but this is independent of Atg7 and canonical autophagy. Atg5 specifically decreases acidification of late endosomes where exosomes are produced, disrupting the acidifying V1V0-ATPase by removing a regulatory component, ATP6V1E1, into exosomes. The effect of Atg5 on exosome production promotes the migration and in vivo metastasis of orthotopic breast cancer cells. These findings uncover mechanisms controlling exosome release, and identify means by which autophagy-related genes may contribute to metastasis in autophagy-independent pathways.
[0231]Exosomes are...
example 2
-Related Gene-5 (Atg5) Controls Exosome Production and Loading with a Network of Autophagy Substrates Independent of Macroautophagy
[0317]Exosomes are extracellular vesicles with emerging roles in tumor invasion and the intercellular spread of proteins including SOD1 and α-synuclein implicated in pathology of neurodegenerative diseases. This Example demonstrates that while exosome release is independent of macroautophagy, altered endosomal acidification abrogates exosome release in cells lacking a subset of genes, like Atg5, which are critical and / or key for macroautophagy. Lack of Atg5 impedes invasion of cancer cells promoted by exosomes. Moreover, Atg5 also controls an alternate fate for an extended network of proteins, including SOD1 and α-synuclein that are normally degraded by autophagy: extracellular release in exosomes. These results demonstrate a mechanism controlling exosome production and contents that may underpin the role of exosomes in cancer cell invasion and the sprea...
example 3
ructs, Exosome Packaging, and Degradation of Neurodegenerative Disease-Related Cellular Targets by Autophagy
[0389]Exosomes as described herein were further investigated for delivering drugs and / or active agents, such as antibodies, from the blood into the brain, and effects thereof were tested. In this Example, LC3 constructs were developed, packaged into exosomes, and delivered to brain cells where degradation of neurodegenerative disease-related cellular targets via autophagy was assessed.
[0390]Extracellular vesicles of ˜100 nm in size, called exosomes, may transfer drugs including, for example, RNA, peptides, and / or proteins, into the brain of pre-clinical animal models. Exosomes may be generated by inward budding of late endosomes to create vesicles inside late endosomes, which are then released to the extracellular space when these late endosomes (or multivesicular bodies) fuse with the plasma membrane. This may result in exosomes with cytoplasmic contents in their interior and...
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