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COMPOSITIONS AND METHODS FOR TREATING METABOLIC DISORDERS
A composition and methods for treating metabolic disorders, such as hepatic steatosis, adipose tissue dysfunction, and insulin resistance. Small interfering RNAs (siRNAs) targeting LPS-binding protein (LBP) that include unlocked nucleotides (UNA) and their therapeutic applications for the treatment of metabolic disorders are provided herein.
-First therapeutic approach using lipid nanoparticles with modified siRNA against liver LPS-binding protein (LBP) for therapy for obesity-associated metabolic disturbances. -LUNAR® system: demonstrated successful, safe and potent siRNA delivery system. -Long term treatment (6 months) with repeated LUNAR®-Lbp UNA-siRNA weekly doses is well tolerated by the mouse liver -Not adverses cytokine profile of mice treated with LUNAR®-Lbp UNA-siRNA in long treated mice -LUNAR®-Lbp UNA-siRNA administration might stimulate tissue macrophage recruitment associated with an anti-inflammatory phenotype