Postdoctoral Researcher, EPFL
Phage Display Selection of Peptides that Resist Proteases in the Gastrointestinal Tract
Oral delivery of peptide or protein drugs poses one of the greatest challenges in the pharmaceutical industry that is currently hampered by the metabolic instability and/or limited intestinal uptake. In this work, we succeeded in generating small-sized (< 1500 Da) high affinity target-specific peptide ligands (Kis < 10 nM) that resist gastrointestinal (GI) proteases. We achieved this by conformationally constraining peptides with chemical bridges and by applying an in vitro evolution procedure with a built-in proteolytic selection process. Peptide orally applied to mice by gavage efficiently resisted proteases in all regions of the GI tract. More than 30% of the applied peptide remained intact and small quantities reached the blood stream. The strategy is the first one that allowed generating target-tailored peptide ligands remaining active in the GI tract, and presents a promising path to generating oral peptide drugs.
Vanessa Carle is a postdoctoral researcher in the field of peptide therapeutics, currently working at Ecole polytechnique fédérale de Lausanne (EPFL).
Vanessa received a Bachelor of Science degree in Biotechnology from University of Pavia, Italy, and a Master of Science degree in Pharmaceutical Biotechnology from Martin Luther University of Halle-Wittenberg, Germany. She then moved to EPFL, Switzerland, where she completed her PhD in Chemical Biology in the laboratory of Prof. Christian Heinis, working on the development of peptide-based inhibitors of coagulation factor XIa for safer anticoagulation.
Her current research focuses on the selection of peptide-based protease inhibitors by Phage Display and hit optimization towards their therapeutic application.