Compositions comprising miR-690 and methods therefor
Inventors
Olefsky, Jerrold M. • YING, Wei
Assignees
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Publication Number
US-12653783-B2
Publication Date
2026-06-16
Expiration Date
Abstract
Compositions comprising miR-690 and methods of employing the compositions are provided.
Core Innovation
miR-690 is identified as an insulin-sensitizing miRNA enriched in alternatively activated (M2) macrophage-derived extracellular vesicles (exosomes). M2 macrophage-derived exosomes containing miR-690 improve glucose tolerance and insulin sensitivity and increase insulin-stimulated AKT phosphorylation. Depletion of exosomal miRNA cargo abolishes these effects, indicating that exosomal miRNA cargo is required for the metabolic improvements.
Synthetic miR-690 mimics delivered to obese models recapitulate insulin-sensitizing metabolic benefits. The disclosure describes functional miR-690 targeting of Nadk/NAD+ kinase-related biology, where miR-690 represses Nadk expression and Nadk knockdown similarly increases insulin signaling.
In a Western diet-induced NASH mouse model, administration of a miR-690 mimic in liposomes reduces steatosis and hepatic inflammation, including macrophage-associated readouts. The disclosure further reports reduced fibrosis with fibrogenic-associated measurements, supporting miR-690 as a therapeutic approach in metabolic disease contexts involving liver pathology.
Claims Coverage
The independent claims cover two inventive features: a synthetic delivery vehicle comprising isolated miR-690 and a method to inhibit or treat insulin resistance, enhance insulin sensitivity, treat metabolic disease, or inhibit Nadk expression by administering isolated miR-690 or a vector encoding miR-690.
Insulin-sensitizing isolated miR-690 delivery vehicle
A synthetic delivery vehicle comprising an insulin sensitizing amount of isolated miR-690 optionally comprising a pharmaceutically acceptable carrier.
Method for inhibiting or treating insulin resistance and/or Nadk expression using miR-690 or a miR-690 vector
A method to inhibit or treat insulin resistance, to enhance insulin sensitivity, to treat metabolic disease, or to inhibit Nadk expression, in a mammal, comprising administering to the mammal an effective amount of a composition comprising isolated miR-690 or a vector encoding miR-690.
Protection is centered on compositions and delivery forms using isolated miR-690, and on therapeutic administration of isolated miR-690 or a miR-690-encoding vector to inhibit insulin resistance, enhance insulin sensitivity, treat metabolic disease, and inhibit Nadk expression.
Stated Advantages
Improves glucose tolerance.
Improves insulin sensitivity.
Increases insulin-stimulated AKT phosphorylation.
Inhibits or treats insulin resistance and/or enhances insulin sensitivity.
Reduces steatosis in a Western diet-induced NASH mouse model.
Reduces hepatic inflammation in a Western diet-induced NASH mouse model.
Reduces fibrosis in a Western diet-induced NASH mouse model.
Documented Applications
Treatment or inhibition of insulin resistance and enhancement of insulin sensitivity in a mammal.
Treatment of metabolic disease in a mammal.
Inhibition of Nadk expression in a mammal.
Use in obesity/HFD contexts to improve glucose tolerance and insulin sensitivity.
Use in a Western diet-induced NASH mouse model to reduce steatosis, hepatic inflammation, and fibrosis.
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