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 Anti-pathogen system and methods of use thereof

Details
Inventors: Dowdy, Steven F.;
Assignee: Washington University (St. Louis, MO)
Primary Examiner: Park; Hankyel T.
Assistant Examiner:
Attorney, Agent or Firm: Buchanan; Robert L., Schray; Kerri Pollard, Corless; Peter F.

The present invention provides an anti-pathogen system comprising one or more fusion proteins that includes a transduction domain and a cytotoxic domain. The cytotoxic domain is specifically activated by a pathogen infection. The anti-pathogen system effectively kills or injures cells infected by one or a combination of different pathogens. Further provided are protein transduction domains that provide enhanced transduction efficiency.

DETAILED DESCRIPTION The present invention relates to an anti-pathogen system that exhibits high transduction efficiency aid specifically kills or injures cells infected by one or more pathogens.
In general, the anti-pathogen system includes a fusion molecule that comprises a transduction domain and a cytotoxic domain genetically and hence covalently linked together as an in-frame fusion molecule.
The invention further relates to transduction domains that enhance the transduction efficiency of the fusion molecules.
The anti-pathogen system is essentially inactive in uninfected cells but it is specifically activated in cells infected by the pathogen.
Further provided are methods of using the anti-pathogen system to treat infection by a pathogen and particularly human pathogens such as certain viruses and plasmodia.
Preferred use of the anti-pathogen system entails that the pathogen infection induce at least one pathogen specific protease.
Preferably, that protease is capable of specifically cleaving a target amino acid sequence.
The target amino acid sequence is one component of the fusion molecule and it is sometimes referred to herein as a protease recognition or cleavage site.
Specific cleavage of the protease recognition site cleaves the fusion molecule, generally at or near the cytotoxin domain, to form a cytotoxin.
The cytotoxin so formed is specifically capable of killing or injuring cells infected by the pathogen.
Significantly, the present anti-pathogen system links formation of the cytotoxin to presence of the pathogen-induced protease, thereby providing highly focussed cytotoxic action to infected cells.
Formation of the cytotoxin is minimized or eliminated in uninfected cells and in infected cells that keep the pathogen inactive.
The anti-pathogen system is therefore capable of effectively and specifically discriminating between productively infected and uninfected cells.
The present anti-pathogen system has a number of important advantages.
For example, it can be readily manipulated to respond to changes in pathogen serotype



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