ANTISENSE OLIGONUCLEOTIDE MODULATORS OF SEROTONIN RECEPTOR 2C AND USES THEREOF

摘要

The present invention provides, among other things, oligonucleotide modulators of human 5′-HT2C receptor (HTR2C) and improved methods and composition for treating HTR2C-related diseases, disorders or conditions based on such modulators. In particular, oligonucleotides modulators according to the invention target specific regions in the Exon V/Intron V junction of the human HTR2C pre-mRNA and drive expression of HTR2C Vb splice isoform, leading to increased generation of non-edited strong HTR2C receptor and enhanced serotonin receptor activity.

主权项

1. An antisense oligonucleotide of 10-50 nucleotides in length comprising a sequence that permits specific hybridization to a target region of a human 5′-HT2C receptor (HTR2C) pre-mRNA under stringent conditions, wherein the target region comprises a nucleotide sequence 5′ UUGGCCAUAAGAAUUGCAGCGGCUAUGCUCAAUACU 3′ (SEQ ID NO: 1) and further wherein the stringent conditions comprise 50% formamide with 1 mg heparin at 42° C. with hybridization carried out overnight and a wash in 0.2×SSC at 65° C. for 15 minutes.