The direct use of recombinant bacteria, or indirectly using bacteriophages, producing and delivering in situ a therapeutic molecule of interest has been extensively described. Many such efforts have also shown high efficacy in animal models but have yet to yield clinical successes, in part because of difficulties in achieving and maintaining sufficiently effective concentrations of the therapeutic molecule at the site of disease. Irrespective of the vector used, a recurring problem to be solved is that of the dose administered of either recombinant bacteria or phage which should be as small as possible, in order to ensure clinical efficacy and lack of toxic side effects. This is an issue since many of the biotherapeutic molecules to be expressed by bacteria are from human origin, and therefore can have folding problems, low stability, low serum half-life, and adverse effects due to multiple cell targets.
To solve these problems, we have developed the concept of foldikines. Foldikines are uniquely modified cytokines with improved properties, and are more amenable to delivery by a therapeutic microorganism. Amongst such improved properties, foldikines show increased stability, higher affinity and specificity for their target receptors, and reduced toxicity, all of which shall translate into greater safety and efficacy in treating human patients.
We have initial evidence (both in vitro and in vivo) of the superiority of foldikines over conventional cytokines, and in this project, we will aim to fully validate the concept and lay the basis for the creation of a new start-up company.
