Nuclease resistant ribozymes with high catalytic activity.

摘要: Abstract Hammerhead ribozymes are efficient RNA enzymes characterized by a typical hammerhead secondary structure and number of conserved bases. Little is known about the role ribose-phosphate backbone, although it obviously important since DNA molecule with same base sequence not catalyst. Here we describe synthesis artificial where modified (2'-O-allyl- 2'-O-methyl-) ribonucleotides substitute for corresponding ribonucleotides. A systematic analysis partially substituted polymers identified minimum set six non-contiguous positions insertion strongly affects catalytic activity. Surprisingly, completely except these still very active. These molecules efficiently cleave in trans target RNAs sequence-specific way, but, unlike ribozymes, resistant to nuclease degradation stable serum. properties make such synthetic potentially useful vivo gene expression studies therapeutic applications.