Ribozyme targeting of HIV-1 LTR.

The 5'-TAR region of HIV-1 mRNA is highly conserved amongst different HIV-1 isolates. We thus investigated the potential for in vivo targeting of the TAR RNA element by a hammerhead ribozyme. The use of the CAT reporter gene linked to the HIV1-LTR, in transient assays, reveals that a hammerhead ribozyme directed towards the first GUC of HIV-1 mRNA can efficiently inhibit CAT protein expression. We show that this inhibition is sequence-specific and probably due to a cleavage activity rather than an antisense effect. We show also that a hammerhead ribozyme that is inactive in vitro is capable of inhibiting CAT protein expression in a cellular environment. These results suggest that the targeting of the HIV-1 LTR by a hammerhead ribozyme constitutes a viable approach for anti-HIV therapy.