Group I aptazymes as genetic regulatory switches

Allosteric ribozymes (aptazymes) that have extraordinary activation parameters have been generated in vitro by design and selection. However, many ribozymes control gene regulation or viral replication in vivo. By appending aptamers to the Group I self-splicing intron, we have generated a Group I aptazyme whose in vivo splicing is controlled by exogenously added small molecules. Substantial differences in gene regulation could be observed with compounds that differed by as little as a single methyl group. Group I aptazymes may find applications as genetic regulatory switches for generating conditional knockouts at the level of mRNA or for developing economically viable gene therapies.