In vitro selection & optimization of synthetic single-domain antibodies
Lieu : Centre Broca Nouvelle-Aquitaine
Invité par Erwan Bezard
Hybrigenics and collaborators have designed a fully synthetic, humanized naïve Llama VHH library containing 3×109 independent VHH clones, based on a unique scaffold with random complementary determining regions (CDRs). A combination of phage display and subsequent yeast two-hybrid (Y2H) or Yeast Display screening is applied to identify VHH nanobodies reactive to native antigens that retain functionality even inside living cells (so-called intrabodies). Also, large proteins, haptens and membrane receptors can be successfully selected from this library.The affinities of our VHH is comparable to the affinity of antibodies selected after animal immunization, but we also present a platform for optimization of VHH from our library or derived from Llama immunization. The VHH clones are directly applicable, but can also be produced as fusions to either human, mouse, sheep or rabbit Fc domains. We will illustrate the capabilities of our platform with an example of selection and optimization of VHH against Tau, to explore the mechanisms underlying tau pathophysiology.
About Jean-Christophe RAIN
Dr Jean-Christophe RAIN received his PhD in Molecular Genetics from University Paris XI. During his PhD thesis at the Pasteur Institute, he was involved in the development of a yeast two-hybrid screening method allowing reproducible analysis of highly complex library by genetically saturated screening. In 1998, Dr. Rain was one of the founders of Hybrigenics where he took over the Head of Small Genome program and generated a genome-wide protein interaction map of Helicobacter pylori. From 2000 to 2005, he was responsible for internal and collaborative target identification and drug discovery programs in oncology and virology. Since 2010, in close collaboration with F. Perez (Curie Institute, Paris), he develop new tools and library for antibody fragment selection in vitro and in yeast. Dr RAIN is currently CSO of Hybrigenics Services SAS, he is leading the Yeast Two-Hybrid, Chemical proteomic and VHH selection platform.