An emerging strategy in the treatment of
viral infections is the use of
antisense DNA or
RNA to pair with, and block expression of viral transcripts.
RNA, in addition to being an informational molecule, can also possess enzymatic activity. Thus, by combining anti-sense and enzymatic functions into a single transcript, it is now possible to design catalytic RNAs, or
ribozymes, which can specifically pair with virtually any
viral RNA, and cleave the phosphodiester backbone at a specified location, thereby functionally inactivating the
viral RNA. In carrying out this cleavage, the
ribozyme is not itself altered, and is thus capable of recycling and cleaving other molecules, making it a true
enzyme. There are several different catalytic motifs which possess enzymatic activity, and each one of these can be incorporated into an enzymatic antisense with site-specific cleavage capabilities. By focusing on one type of catalytic motif, the hammerhead, we describe the principles behind the development of
ribozymes as transacting, site-specific
ribonucleases, several applications of
ribozymes in functional destruction of target RNAs, as well as several of the problems confronting their use. We also describe a
liposome delivery system which facilitates intracellular inclusion of
ribozymes, and may provide a means for therapeutic delivery of
ribozymes to HIV-1 infected cells.