INHIBITION OF MOLONEY MURINE LEUKEMIA-VIRUS BY A RETROVIRAL VECTOR, LNL6, CARRYING RIBOZYMES TARGETED TO THE 5'-NONCODING SEQUENCE

The packaging region Psi is the RNA sequence which directs the inclusi on of genomic viral RNA into virions. As such it represents an apparen tly accessible site for ribozyme action. Ribozymes directed against th e Psi site of Moloney murine leukaemia virus (MoMLV) were delivered to target cells using a related retroviral vector, LNL6. LNL6 is a vecto r predominantly derived from MoMLV and, like all retroviruses, require s the Psi region to be packaged, By exploiting the heterogeneity betwe en nucleotide sequences of the MoMLV target and LNL6 vector in the Psi packaging region, two ribozymes were designed and shown to selectivel y cleave the target but not the vector sequence. Clonally derived cell lines expressing ribozymes showed inhibition of virus replication. Th ese results show the utility of catalytic RNA as specific antiviral ag ents.