Solving Traffic Jam in Protein Secretion

Over the past two decades, the demand for therapeutic proteins is continuously increasing. Recombinant protein therapeutics have been developed to treat a wide variety of clinical indications such as metabolic, immunologic or genetic disorders and different kinds of cancer. The majority of the therapeutic proteins are produced by secretion, although in many cases the secretion yield is insufficient. We are targeting the secretion problem using two strategies. First, we characterize the factors which affect the secretion such as the hydrophobicity distribution of the protein sequence and its propensity to fold into secondary structures, using an algorithm we based on high throughput screens and deep sequencing. The other strategy is to design a bacterial-based system that will allow us to test point mutations that may improve the translocation of a target protein. The analysis is based on initial detection of hydrophobic motifs followed by identification of orthologues that do not contain these hydrophobic motifs, and finally introduce conserved mutations to interrupt the hydrophobic motif, while taking in account the protein’s structure and activity restrictions. Our first targets are viral envelop proteins useful for anti-viral vaccination.