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Licensing opportunity DI 05/18

Methods for detecting virulent Plasmodium for evaluating Plamodium virulence, and for screening new drugs employing the 3’UTR of Plasmodium SUB2 and the Plasmodium SUB2 serine protease

Inventors: Jean-Christophe BARALE et al.

Description of invention: 

Proteases are known to play crucial role in various infectious or cancerous pathologies and have been successfully defined as chemotherapeutic targets : the specificity of these enzymes allows the selection of highly specific inhibitors which block the pathologic process without considerable toxic side effects. Interestingly, biochemical and genetic analyses have shown that proteases, and particularly serine proteases, play a central role for both the liberation and the entry of the merozoites into the host red blood cell (RBC).
Compared to intra-erythrocytic parasite stages, the merozoite, is briefly free in the plasma, thus being directly accessible to external factors such as antibodies or chemical drugs. These observations suggested that parasite serine proteases involved in RBC and hepatocytes invasion are potential targets for new anti-malarial molecules.
SUB2 can be defined as a maturase whose activity is critical for the biological cycle of malaria parasites, and be seen as a seduced putative anti-malaria drug target.

 Potential applications

 Screening of new anti malarial drugs.
 Patent status

 US regular patent application filed on May 3rd, 2005 (US 11 / 119,826)
 PCT application filed on May 3rd, 2006 (PCT / IB2006 / 001918)

 Gene targeting demonstrates that the Plasmodium berghei subtilisin PbSUB2 is essential for red cell invasion and reveals spontaneous genetic recombination events.
Uzureau P, Barale JC, Janse CJ, Waters AP, Breton CB.
Cell Microbiol. 2004 Jan ; 6(1):65-78.

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