Protein-based therapies using quantitatively designed proteins
A bipartite, quantitatively designed protein having two discrete ligands and a linker; one ligand having the ability to strongly bind to a particular cell, the other having the ability to affect a target only when the previous ligand binds.
For many years, researchers have tried to construct bipartite proteins with properties that derive from each moieties parental source. A universal problem with this kind of approach is that the likelihood of off-target effects as the drug travels through the body is high.
Because reaction rates are often enhanced by reduction of space between two substrates, researchers thought that an initial rapid binding reaction to one cell surface protein could drive a second, weak interaction on the same cell surface, driven solely by reduction in space.
It is believed that it is possible to tune the binding affinities of both the targeting agent and the activating ligand appropriately, allowing the development of a mutant protein that would show negligible activation on cells expressing just one of the relevant receptors.
Proof of principle has been demonstrated using EGF as the targeting agent and IFN?-2a as the ligand and research continues using the same technology for the development of bipartite haemopoietic, asthma, and HIV therapeutics.
Intellectual Property Status: Patent(s) Pending
Bipartite therapeutics, in addition to the method of quantitative design, is available for worldwide licensing on an exclusive basis. The Silver lab is interested in identifying bipartite therapeutics for a number of indications including anemia, asthma, and RA and is interested in accessing additional resources to support these efforts.