Innovir Laboratories, Inc.

Andy Shih

Shaji T George

Jeffrey Michael Bockman

Regulatable RNA molecules such as regulatable ribozymes, nucleic acids encoding such regulatable ribozymes, and methods of making and using such regulatable ribozymes are disclosed. Regulatable ribozymes comprise a ligand-binding RNA sequence and a ribozyme sequence capable of cleaving a separate targeted RNA sequence, wherein upon binding of the ligand to the ligand-binding RNA sequence, the activity of the ribozyme sequence against the targeted RNA sequence is altered. The ligand may be either an inorganic or an organic molecule and may be a co-drug which can be administered to specifically regulate the ribozyme activity. Regulatable RNA molecules other than ribozymes are also disclosed, such as regulatable mRNA molecules which comprise a ligand-binding RNA sequence separate from the coding sequence, wherein upon binding of a ligand to the ligand-binding RNA sequence, translation of the regulatable mRNA is altered.

Regulatable RNA molecule

Regulatable nucleic acid therapeutic and methods of use thereof

A system is described for the use of a ribozyme as a diagnostic tool for detecting the presence of a nucleic acid, protein, or other molecule, in which the formation of an active ribozyme and cleavage of an assayable marker is dependent on the presence or absence of the specific target molecule. The essential component is a ribozyme specifically but reversibly binding a selected target in combination with a labelled co-target, preferably immobilized on a support structure. When both the target and co-target are bound, the ribozyme cleaves the label from the co-target, which is then quantifiable. Since the ribozyme is reversibly bound by target and co-target, it can reassociate with additional co-target, cleaving more label, thereby amplifying the reaction signal. In one embodiment, the target is a nucleic acid hybridizing to complementary sequences that form part of the ribozyme; in a second embodiment, the target is a protein or other macromolecule which is bound by interactions with a portion of the ribozyme molecule in another embodiment, a thermostable ribozyme is used, so that improperly bound ribozyme is destabilized and inactive at elevated temperatures. A method for isolating regularable ribozymes is also disclosed. The regulatable ribozymes are useful in the method for detecting the presence of a specific macromolecule, or can be used in in vitro or in vivo methods for inactivation or activation of the cleavage of target RNA molecules.

Growing community of inventors

New York, NY, United States of America

Andy Shih