Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9034839-B2
Publication Date
2015-05-19
Expiration Date
Abstract
Provided are novel methods and compositions for the modulation of thermogenesis. Such methods are particularly advantageous in that they allow for the reduction of body fat in a subject without the subject having to adjust their caloric intake through dieting, modify their physical activity or undergo bariatric surgery. Accordingly, the methods of the invention are particularly useful for treating or preventing obesity. Also provided are methods of screening for novel agents that modulate the activity of thermogenic regulators.
Core Innovation
The invention relates to using isolated miRNA agents to modulate thermogenesis in a tissue and respiratory chain uncoupling in a cell. The approach contacts the cell or tissue with a miRNA agent that increases activity of at least one mitochondrial uncoupler selected from UCP1 or UCP2, and hsa-miR-515-3p or an agomir thereof is identified as the specified miRNA agent.
The document frames the problem as needing methods for treating or preventing obesity by modulating thermogenesis and/or respiratory chain uncoupling. It describes direct or indirect modulation of thermogenic pathways, including multi-targeting and modulation of thermogenic-regulator activity through changes in activity and/or expression of relevant mRNA and proteins.
Thermogenic regulation is supported by UCP1 as a central downstream thermogenic regulator, including regulatory elements in the promoter region, 5′UTR, 3′UTR, and coding sequence, and predicted miRNA binding sites. The document further describes miRNA target relationships and provides miRNA target and sequence information to support identification of interactions relevant to thermogenesis and mitochondrial uncoupling.
The invention also describes identifying miRNA agents that alter thermogenic-regulator activity using screening methods with indicator cells. In addition, cell- and tissue-specific delivery concepts are described through targeting moieties, including aptamers, that deliver the miRNA agent to a specific cell type or tissue.
Claims Coverage
The provided claim coverage includes 2 key inventive features in the independent method claim: a specific miRNA agent and increased activity of mitochondrial uncouplers UCP1 or UCP2 to modulate respiratory chain uncoupling or thermogenesis.
MiRNA agent increases UCP1 or UCP2 activity for respiratory uncoupling or thermogenesis
A method of modulating respiratory chain uncoupling in a cell or thermogenesis in a tissue by contacting the cell or tissue with a miRNA agent that increases activity of at least one mitochondrial uncoupler selected from UCP1 or UCP2.
Hsa-miR-515-3p or an agomir thereof
The miRNA agent is hsa-miR-515-3p or an agomir thereof.
The claim coverage centers on contacting a cell or tissue with an hsa-miR-515-3p, or agomir thereof, to increase activity of mitochondrial uncouplers UCP1 and/or UCP2, thereby modulating respiratory chain uncoupling or thermogenesis.
Stated Advantages
Treat or prevent obesity by modulating thermogenesis and/or respiratory chain uncoupling.
Documented Applications
Modulating respiratory chain uncoupling in a cell and thermogenesis in a tissue, for treating or preventing obesity.
Interested in licensing this patent?