Bulk Reformatting of Antibody Fragments Displayed on the Surface of Yeast Cells to Final IgG Format for Mammalian Production

Methods Mol Biol. 2023:2681:291-311. doi: 10.1007/978-1-0716-3279-6_16.

Abstract

While yeast surface display (YSD) has gained traction for antibody hit discovery efforts with the first therapeutic YSD-isolated antibody sintilimab approved in 2018, a major drawback that remains is the time-consuming reformatting of monoclonal antibody (mAb) candidates. By using a Golden Gate cloning (GGC)-dependent workflow, the bulk transfer of genetic information can be performed from antibody fragments displayed on yeast cells to a bidirectional mammalian expression vector. Herein, we describe in-depth protocols for the reformatting of mAbs, starting from the generation of Fab fragment libraries in YSD vectors and ending up with IgG molecules in bidirectional mammalian vectors in a consolidated two-pot, two-step procedure.

Keywords: Antibody hit discovery; Antibody reformatting; Golden Gate Cloning; Yeast surface display.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / metabolism
  • Genetic Vectors
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Mammals / genetics
  • Peptide Library*
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Peptide Library
  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G