Biofocus Discovery Limited

Medical Research Council

Mark P Chadwick

Stephen James Russell

Christian Buchholz

Stephen J Russell

Frances Joanne Bullough

Methods are disclosed whereby inhibition of proteolytic activity causes an increase in delivery of a transferable label from a viral display package to a target cell. Assaying for the transferable label in the target cell in the presence of a test substance can identify the test substance as a protease inhibitor. Protease inhibitors so identified are used therapeutically, to treat conditions such as cancer, inflammation, rheumatoid arthritis and other autoimmune diseases, and infections, including AIDS, herpes, and hepatitis.

Methods for identifying a protease inhibitor

Methods are disclosed whereby protease activity is directly linked to replication of viral display packages containing protease-encoding polynucleotides in target cells. The methods can be used, inter alia, to identify proteases, including previously undiscovered proteases or variants of known proteases which may have altered substrate specificity.

Methods and compositions for identifying a protease

Methods are disclosed whereby protease activity is directly linked to delivery of a transferable label to a target cell which expresses a protease, via fusion of viral display packages comprising the transferable label with the target cell. The methods can be used, inter alia, to identify proteases, including previously undiscovered proteases or variants of known proteases which may have altered substrate specificity.

Methods and compositions for identifying a polynucleotide encoding a protease

Disclosed is a method of testing a substance for the ability to affect the formation or oligomerization of a complex comprising members of a specific binding pair, a first member of the binding pair being present on the surface of a lipid enveloped particle comprising a transferrable label, said first member of the binding pair being capable of binding to a second member of the specific binding pair present on the surface of a cell, the lipid envelope of the particle being capable of fusing with the membrane of the cell so as to transfer the label to the cell, said transfer being inhibited by formation or oligomerization of a complex between the first and second members of the binding pair, wherein the method comprises reacting the particle and the cell, in the presence of the substance under test, (under conditions which would allow for binding of the first and second members of the specific binding pair in the absence of the substance under test), and detecting the label transferred, if any; together with a composition for use in the assay method of the invention.

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Cambridge, United Kingdom

Mark P Chadwick