摘要 |
Disclosed is a novel class of molecules referred to herein as sitoxins (signalrelated, cleavage-mediated toxins. A sitoxin combines several functional domains to produce a therapeutically effective molecule. More specifically, a sitoxin is comprised of an effector domain; a domain bearing an intracellular signalling moiety; and a domain located between the effector domain and the domain bearing the intracellular signalling moiety which specifies a cleavage site for a predetermined protease. Also disclosed are methods for selectively killing a target cell which is known to contain a predetermined protease. Such methods involve the introduction of a sitoxin into a target cell. The sitoxin can be introduced directly, or through the intermediacy of an expression vector. Following the introduction of the sitoxin into the target cell, cleavage by the predetermined protease separates the effector domain of the sitoxin from the intracellular signalling moiety, resulting either in a longerlived (and therefore more toxic) effector domain or in an effector domain that moves from a cellular compartment where the domain is nontoxic to a cellular compartment where the domain is able to exert its effect.
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