The packaging region psi is the RNA sequence which directs the inclusion of genomic viral RNA into virions. As such it represents an apparently accessible site for ribozyme action. Ribozymes directed against the psi site of Moloney murine leukaemia virus (MoMLV) were delivered to target cells using a related retroviral vector, LNL6. LNL6 is a vector predominantly derived from MoMLV and, like all retroviruses, requires the psi region to be packaged. By exploiting the heterogeneity between nucleotide sequences of the MoMLV target and LNL6 vector in the psi packaging region, two ribozymes were designed and shown to selectively cleave the target but not the vector sequence. Clonally derived cell lines expressing ribozymes showed inhibition of virus replication. These results show the utility of catalytic RNA as specific antiviral agents.


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