Antiviral ribozymes

Abstract

Catalytic RNAs are a genetic property not only of some particular viroids or viruses, but also are more common naturally among eukaryotes and even prokaryotes than earlier expected. However, the major interest in ribozymes results from their potential for development of "tailor-made" cDNA constructions designed to be transcribed into catalytic RNAs that will recognize by hybridization and destroy by specific cleavage their cellular or viral RNA targets. The efficiency of an antiviral ribozyme is determined by both the accessibility and sequence conservation of the target region, as well as the design of the ribozyme: its type, size, and composition of flanking sequences; expression rates; and cellular compartment localization. Until now the most frequently selected viral target is the human immunodeficiency virus, where an up to a 10(4)-fold inhibition in its progeny production has been achieved. Although the first generation ribozymes focused on improvements in basic design and expression rates, more recently the efficiency of antiviral catalytic activity has been increased by employing polyribozymes and/or multitarget ribozymes, as well as special constructions to enhance the cellular co-compartmentation of the ribozyme with its viral RNA target.

Disruption of dengue virus transmission by mosquitoes

“…For example, the use of tRNA valine pol III as the promoter allows hRz expression to reach levels high enough to help overcome the rate-limiting step for catalysis in cells, the binding of the ribozyme to its target [69]. The clover leaf structure of the tRNA enables the protein exportin-X to transport the hRz to the cytoplasm, where it co-localizes with the infecting viral RNA and causes its degradation before the viral RNA has the opportunity to replicate (and to produce progeny RNA genomes) in the cell [70]. Target site accessibility is enhanced by attaching an Adenosine 60 tail to the hRz, allowing recruitment of RNA helices that can unwind potential interfering secondary structures in the target viral RNA (Figure 2) [71–74].…”