02388nas a2200205   4500008004100000245014100041210006900182260000800251300001400259490000700273520164000280100001701920700001801937700002301955700002001978700002001998700001902018700001802037856012702055       2016                        eng d00aSystematic evaluation of biophysical and functional characteristics of selenomethylene-locked nucleic acid-mediated inhibition of miR-210 aSystematic evaluation of biophysical and functional characterist  cDEC  a7023-70320 v553 amiRNAs constitute an important layer of gene regulation mediated by sequence-specific targeting of mRNAs. Aberrant expression of miRNAs contributes to a host of pathological states. Promoting cancer, miR-21 is upregulated in variety of cancers and promotes tumor progresion by suppressing a network of tumor suppressor genes. Here we describe a novel class of bicyclic RNA analogues, selenomethylene-locked nucleic acid (SeLNA), that display high affinity, improved metabolic stability, and increased potency for miR-21 inhibition. The thermal stability (T-m) for duplexes was increased significantly with incorporation of SeLNA monomers as compared to that of the unmodified DNA RNA hybrid. A comprehensive thermodynamic profile obtained by isothermal titration calorimetry revealed a favorable increase in the enthalpy of hybridization for SeLNA containing DNA and target RNA heteroduplexes. SeLNA modifications displayed remarkable binding affinity for miR-21 target RNA with a K-a of <= 1.05 x 10(8) M-1. We also observed enhanced serum stability for SeLNA RNA duplexes with a half-life of <= 36 h. These in vitro results were well correlated with the antisense activity in cancer cells imparting up to similar to 91% inhibition of miR-21. The functional impact of SeLNA modifications on miR-21 inhibition was further gauged by investigating the migration and invasion characterisitics of cancer cells, which were drastically reduced to similar to 49 and similar to 55%, respectively, with SeLNA having four such modifications. Our findings demonstrate SeLNA as a promising candidate for therapeutics for disease associated miRNAs.1 aNahar, Smita1 aSingh, Amrita1 aMorihiro, Kunihiko1 aMoai, Yoshihiro1 aKodama, Tetsuya1 aObika, Satoshi1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/systematic-evaluation-biophysical-and-functional-characteristics-selenomethylene-locked