siRNA Modified with 2′‐Deoxy‐2′‐C‐methylpyrimidine Nucleosides |
| |
| Authors: | Dr María Dellafiore Dr Anna Aviñó Adele Alagia Dr Javier M Montserrat Dr Adolfo M Iribarren Prof Dr Ramon Eritja |
| |
| Affiliation: | 1. INGEBI (CONICET), Buenos Aires, Argentina;2. Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC), Barcelona, Spain;3. NetworkingCenter on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain;4. Instituto de Ciencias, Universidad Nacional de General Sarmiento, Los Polvorines, Prov. Buenos Aires, Argentina;5. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina;6. Laboratorio de Biotransformaciones, Universidad Nacional de Quilmes, Bernal, Prov Buenos Aires, Argentina |
| |
| Abstract: | (2′S)‐2′‐Deoxy‐2′‐C‐methyluridine and (2′R)‐2′‐deoxy‐2′‐C‐methyluridine were incorporated in the 3′‐overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)‐2′‐deoxy‐2′‐C‐methylcytidine was incorporated in the 6‐position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3′‐overhang region by (2′S)‐ or (2′R)‐2′‐deoxy‐2′‐C‐methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity. |
| |
| Keywords: | deoxymethylpyrimidine bases nucleosides siRNA stability structure– activity relationships |
|
|
