Science

SCIENCE OF APTAMERS & THEIR SPECIFIC ACTIVE CONTROL AGENTS

Aptamers are synthetic macromolecules that can adopt a unique three-dimensional shape and bind specifically and tightly to a target molecule.

Regado’s aptamer-based therapeutics are identified using a proprietary in vitro selection process known as SELEX (Systematic Evolution of Ligands by EXponential enrichment), which the Company in-licensed from Archemix Corporation.  In the SELEX process, a vast library of oligonucleotide sequences are incubated with a specific target protein and nucleic acid aptamers with the optimal structural and binding properties are isolated.  Aptamers have been discovered that can bind to essentially every class of therapeutic protein target.

Once elucidated, an aptamer’s nucleotide sequence can be used to design an active control agent in the form of an oligonucelotide complementary to the nucleotide sequence of the aptamer, as discovered by Drs. Bruce Sullenger and Chris Rusconi of Duke University in the early 2000s.  An aptamer and its active control agent bind via nucleotide base pairing, triggering a structural change in the aptamer that causes its release from the target protein, negating the aptamer’s therapeutic effect.  Based upon the dose of active control agent administered, the activity of an aptamer can be fully neutralized, or titrated to intermediate levels in a tightly controlled manner.

Pioneering research on this approach to modulating the therapeutic activity of nucleic acid aptamers was published in Nature in September 2002, and Regado subsequently licensed the technology from Duke University.  By combining this technology with the SELEX discovery process, Regado has created a powerful platform for the discovery of aptamer control agent systems.