Nuclease resistant ribozymes with high catalytic activity

G. Paolella, B. S. Sproat, A. I. Lamond

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    148 Citations (Scopus)


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

    Original languageEnglish
    Pages (from-to)1913-1919
    Number of pages7
    JournalEMBO Journal
    Issue number5
    Publication statusPublished - 1 May 1992


    • 2'-O-alkylribonucleotides
    • Hammerhead
    • Ribonucleotide analogues
    • Ribozymes
    • RNA catalysis

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Biochemistry,Genetics and Molecular Biology
    • General Immunology and Microbiology


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