Improved serum stability and biophysical properties of siRNAs following chemical modifications.
Small interfering RNAs (siRNAs) which mediate sequence-specific gene silencing through RNA interference have been harnessed for therapeutic applications. Here, we found combinations of modest 2'-ribose siRNA modifications that permit effective gene silencing and improve siRNA stability in human serum. Introduction of as few as two different or identical 2'-ribose modifications at a specific position of either strand, which has been previously suggested to suppress unintended off-target effects, enhances the thermal and thermodynamic stability of siRNA duplexes, and does not alter the overall A-form helical geometry that is required for silencing activity. Our results provide a useful template for the design for therapeutic siRNAs.
Cho
Ik Sang
IS
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, South Korea.
Kim
Jung
J
Lim
Do Hwan
DH
Ahn
Hee-Chul
HC
Kim
Hyunggee
H
Lee
Kang-Bong
KB
Lee
Young Sik
YS
D015153:Blotting, Western; D002942:Circular Dichroism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009691:Nucleic Acid Denaturation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000097:blood* / Q000737:chemistry* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012266:Ribose / Q000737:chemistry; D044967:Serum / Q000737:chemistry; D013816:Thermodynamics; D014162:Transfection
D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D012266:Ribose