Obesity and associated cardio-metabolic disorders are multifactorial diseases that cannot be easily controlled by classical therapeutic agents (Mechanism of Action: one drug-one target or one drug-two/three targets).
AptamiR’s approach uses a pleiotropic concept (One Drug-Multiple Targets) by developing oligonucleotide therapeutics targeting microRNAs, as they simultaneously modulate many target genes involved in lipid oxidation, mitochondrial activity and energy expenditure, This One Drug-Multiple Targets concept is most appropriate for complex and multi-factorial diseases like diabesity and MAFLD.
miR-22-3p modulates several target genes involved in lipid oxidation, mitochondrial functions, thermogenesis, glucose metabolism, adipocyte differentiation, inflammation and anti-oxidation:
Validation of miR-22-3p as a “metabolic target”.
Using various in silico, in vitro and in vivo tools, we demonstrated that miR-22-3p is an excellent metabolic target that modulates several genes as illustrated below with:
- metaMIR (http://rna.informatik.uni-freiburg.de) which ranks miRNAs in relation to gene networks:
- the Protein-Protein Interaction Functional Enrichment Analysis Tool STRING (https://string-db.org) illustrating various interactions within the network of proteins related to miR-22: