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Review
. 2000 Nov;106(10):1197-202.
doi: 10.1172/JCI11631.

Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics

N Usman  1 , L M Blatt
Affiliations
Review

Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics

N Usman et al. J Clin Invest. 2000 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Structure of a general nuclease-resistant ribozyme bound to a generic target RNA. The ribozyme consists primarily of 2′-O-Me nucleotides (lower case). The 3′ and 5′ ends are protected by an inverted 3′-3′ deoxyabasic sugar (iB) and four phosphorothioate linkages (s), respectively. The five purine nucleotides (rA or rG) in the catalytic core (shown in green) are required for catalytic activity. A single non-natural carbon containing pyrimidine analog (2′-C-allyluridine) at U4 was used to stabilize the core and maintain activity. The ribozyme binds its cognate target via Watson-Crick base-pairing. In the target strand, cleavage takes place 3′ to the unpaired nucleotide H (H = A, C, or U). This type of ribozyme has an ex vivo serum t1/2 = 10 days.
Figure 2
Figure 2
Inhibition of colorectal cancer metastases to the liver by ANGIOZYME. The number of metastases to the liver 41 days after intrasplenic inoculation of KM12L4a cells is shown. ANGIOZYME was administered by continuous s.c. infusion for 28 days starting on day 3 after inoculation. Details are described in ref. . AP < 0.05.
Figure 3
Figure 3
Efficacy and mechanism of action of an anti-HCV ribozyme. Treatment of cells infected with HCV-poliovirus, using a ribozyme (HEPTAZYME) directed at site 195 of the HCV genome, results in a significant, approximately 90% inhibition of replication (P < 0.01), while treatment with either a SAC or a BAC results in no inhibition of viral replication.
See this image and copyright information in PMC

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