Table 3.
Ribozymes and deoxyribozymes used for cancer suppression
Ribozymes | |||||||
---|---|---|---|---|---|---|---|
mRNA target | Type of cancer | Cell culture/animal model/phase of clinical study | Nucleic acid modifications | Tumor delivery | Off-target effects | Reference | |
In vivo (animal models) | ft-1 vascular endothelial growth factor (VEGF) | numerous human tumor types | Cynomolgus monkeys, mice | 4 phosphorothioate bonds and an inverted 3'-3' deoxyabasic sugar in one of the recognition arms | intravenously, subcutaneously |
None | 135 |
HERZYME HER-2/neu |
breast cancer | nude mice | 4 phosphorothioate bonds and an inverted 3'-3' deoxyabasic sugar in one of the recognition arms | subcutaneously | None | 136 | |
Clinical studies | ft-1 vascular endothelial growth factor (VEGF) | breast and colorectal cancer | Phase I, multidose phase I/II, phase II | 4 phosphorothioate bonds and an inverted 3'-3' deoxyabasic sugar in one of the recognition arms | intravenously, subcutaneously |
None | 137,138 |
HERZYME | breast cancer | Phase I | 4 phosphorothioate bonds and an inverted 3'-3' deoxyabasic sugar in one of the recognition arms | subcutaneously | None | 139 | |
Deoxyribozymes | |||||||
mRNA target | Type of cancer | Cell culture / animal model / phase of clinical study | Nucleic acid modifications | Tumor delivery | Comments | Reference | |
In vivo (animal models) |
c-jun | nodular basal-cell carcinoma | primates, mice | - | intravenously | Off-target: activation of inhibitor of caspase-activated deoxyribonuclease and protein kinase C delta | 144,145 |
MMP-9 | normal and transgenic mice | - | None | 148 | |||
EGR-1 | breast carcinoma | nude mice | - | intratumoral | None | 149 | |
Clinical studies | c-jun | nodular basal-cell carcinoma | phase I | - | intratumoral | None | 146 |
EBV-LMP1 | Nasopharyngeal carcinoma | phase I | phosphorothioate-modified “10-23” DNAzymes | intravenous administration | None | 147 |