Ribozymes: A New Frontier in Anti-HIV Strategy

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Abstract
A recent addition to the arsenal of antiviral agents are small, single-stranded catalytic RNAs (ribozymes) capable of specific destruction of target RNAs, leading to their functional inactivation. These dual features–substrate specificity inherent in nucleic acid complementarity coupled with catalytic degradation of the bound substrate–are analogous to sophisticated antisense oligonucleotides having restriction enzyme properties. Ribozymes fulfill certain criteria critical to the design of effective antiviral agents in (1) having the ability to interrupt a critical step early in the virus replication cycle before the virus has extensively damaged cellular machinery; (2) having sufficient specificity to interfere with critical viral functions without affecting host processes; and (3) having activity against a variety of viral strains generated throughout the course of the infection, especially for highly mutable pathogens, such as HIV. Several reports have now demonstrated the capability of molecularly tailored ribozymes to block gene expression by specifically cleaving the cognate RNA transcript.