Extremely potent and well-referenced in vivo LNA™ microRNA inhibitors with low toxicity
LNA™ oligonucleotides have higher affinity for their targets than regular DNA or RNA based oligonucleotides. The LNA™ technology has been successfully applied in vivo
, combining low concentrations of the microRNA inhibitor with high serum stability and low toxicity. in vivo
miRCURY LNA™ microRNA inhibitors are so potent that effective microRNA inhibition has been achieved with buffered saline oligonucleotide solutions in a broad range of organs and tissues (Figure 1).
Effective knockdown in a broad range of animals by simple administration routesin vivo
LNA™ microRNA inhibitors have been used successfully in various animal models – small rodents, primates and even in humans. No special formulation or packaging in nanoparticles or lipid based transfection reagent is required. The most frequently used routes of administration are intravenous (through the tail vein in mice), intraperitoneal and subcutaneous. All three methods give similar biodistribution with most of the oligonucleotide accumulating in the liver and kidney. In general, we recommend subcutaneous administration because it is easy and can be repeated many times and in addition this method is associated with little discomfort to the treated animals.
Administer at low doses down to 5 mg/kg
The required dose regime varies with the target organ and animal model. In mice reported dose regimes range from 5-25mg/kg once or twice per week. Different types of local administration have been used successfully, such as oropharyngeal intratracheal instillation (lungs) and retro-orbital administration (eye). Oligonucleotides do not normally cross the blood-brain barrier and delivery to the brain requires intercranial surgery or alternatively administration into the cerebrospinal fluid.
List of selected scientific publications with in vivo miRCURY LNA™ microRNA Inhibitors:Bhagat et al.
miR-21 mediates hematopoietic suppression in MDS by activatingTGF-β signaling. Blood. 2013, 121(15):2875-81. Boon et al.
MicroRNA-34a regulates cardiac ageing and function. Nature. 2013, 495(7439):107-10. Hollander et al.
Striatal microRNA controls cocaine intake through CREB signalling. Nature. 2010, 466(7303):197-202. Kornfeld et al.
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature. 2013, 494(7435):111-5. Ng et al.
A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. J Clin Invest. 2012, 122(3):1097-108. Pencheva et al.
Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 2012, 151(5):1068-82. Seeger et al.
Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice. Obesity (Silver Spring). 2014, 22(11):2352-60. Sene et al.
Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013, 17(4):549-61. Son et al.
The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis, Nat Commun. 2013, 4:3000. PMID: 24346612