Immunotherapy for Infectious Diseases

Gene Therapy for HIV-1 Infection 243
Fig. 3. Schematic representation of two ribozymes to block HIV-1 replication. The structures
shown are paired with actual HIV-I target sequences. (Top) A hammerhead ribozyme pairs
specifically with a sequence in the gag region of the HIV-1 genome. (Bottom) A hairpin
ribozyme designed to bind to and cleave the 5� end of the viral genome, abolishing the reverse
transcription and integration of progeny virus.
and ribozymes in that mutant Tat or Rev, which will not bind to the RNA decoys, will
also not bind to their actual targets. Thus, the likelihood that mutant strains would arise
that would bypass the RNA decoy trap is low.
Combination Therapies
The question still needs to be addressed of whether mutant forms of the HIV-1 virus
could arise that would eventually escape the blocking genetic antiviral. In addition,
increased multiplicities of infection seem to overwhelm most gene therapeutic
approaches toward inhibiting HIV-1 replication. Thus new approaches toward augmenting
the anti-HIV-1 activities of single genetic antivirals are being developed, and
experiments are under way in many laboratories to test the therapeutic effect of a combination
of two or more anti-HIV-1 antivirals. For example, combinations of different
ribozymes (i.e., an RRE decoy with RevM10 and a ribozyme) were more efficient
blockers of HIV-1 replication than either genetic antiviral alone. Furthermore, it has
been reported that a combination of conventional anti-HIV-1 drugs with genetic antivirals
inhibits HIV-1.