Studies on Modified Oligonucleotides

Abstract

A series of isonucleotide incorporated antisense oligodeoxynucleotides have been synthesized, in which isonucleotide was introduced at different positions of the sequences. The results showed that though the incorporated isonucleotides at different position of the sequence interfered in the binding ability in different extent, B-form duplexes were maintained and the binding abilities of the 3′-end modified duplexes were better than the corresponding mismatched duplexes. The DNA/RNA hybrid formed by modified oligodeoxynucleotide and its target RNA could activate the activity of RNase H. The 3′-end modified antisense oligodeoxynucelotides showed the inhibition on S glycoprotein expression of SARS-CoV at the mRNA levels in insect Sf9 cells. In this presentation, a novel class of amino-isonucleoside was synthesized and incorporated into different positions in the sense or antisense strand of siRNA duplexes. The 3′ and 5′ sense strand aminonucleoside modified siRNAs (ssISO-siRNA1 and ssISO-siRNA2) showed the similar duplex thermal and serum stability as natural one and the luciferase activities showed that such modified siRNA is compatible with the intracellular siRNA machinery.

Keywords:

• Isonucleoside
• aminonucleoside
• siRNA
• antisense oligodeoxynucelotide

Acknowledgments

This work was supported by the National Natural Science Foundation of China 20332010 and SFCBIC 20320130046), the Ministry of Science and Technology of China 2005BA711A04) and Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD200265).