The design of evolution and the evolution of design: Binding molecules in biomedicine - CH637
Event details
| Date | 29.04.2025 |
| Hour | 16:15 › 17:15 |
| Speaker | Prof. Andreas Plückthun |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Abstract :
The lecture will highlight designed binding proteins and concentrate on two application areas.
First, to enable in vivo production of therapeutic proteins, we have combined several protein engineering technologies to devise a new platform, termed SHielded, REtargeted ADenovirus (SHREAD). It is based on virus-like particles that are devoid of any viral genes, but contain 36 kb of DNA that can encode multiple genes and complex regulatory regions. To target particular cells and organs, an adapter strategy has been devised, based on the DARPin platform, to selectively target any surface receptor of interest. To hide the particles from the immune system and to minimize liver targeting, a protein shield was developed covering the particles.
In vivo applications have included expressing therapeutic anti-tumor antibodies, therapeutic cytokines or bispecific T-cell engagers in situ, as well as infecting and reprogramming T-cells in vivo, and targeting of dendritic cells in lymph nodes to co-express cytokines there for highly efficient tumor vaccination.
Second, we challenge the paradigm of selection from large universal libraries to obtain binding proteins rapidly and efficiently — and we also challenge the paradigm of individually de novo designing each binder for each target. When it comes to linear epitopes, we found it possible to exploit the periodicity of peptide bonds and create a completely modular system, based on a binding protein design that shares the same periodicity, using Armadillo Repeat Proteins.
Using orthogonal approaches of design, selection, evolution, biophysical testing, and structure determination, significant progress has been reached toward the creation of a system of modular binding proteins that are modular and complementary to a given peptide sequence. We believe that this technology can provide a new paradigm of creating binding proteins for many challenges in biomedical research.
Biography:
Andreas Plückthun has been Professor of Biochemistry at the University of Zürich, Switzerland since 1993. He studied chemistry at the University of Heidelberg (Germany). He received a PhD from the University of California at San Diego in 1982 (with Ed Dennis), was postdoctoral fellow at Harvard University (1982-85) (with Jeremy Knowles) and from 1985 until 1993, group leader at the Gene Center and Max-Planck-Institute for Biochemistry in Martinsried near Munich.
He has written over 500 publications, which have been cited over 50,000 times (h-index 130) [Google Scholar]. In 2003, he was elected to the German Academy of Science. In 1992, he was elected member of EMBO.
He received, among others, the 2016 Christian-Anfinsen Award of the Protein Society for "pioneering contributions to protein engineering", and the Swiss Technology Award 2005 (Bern, Switzerland) and the deVigier Award in 2005, the JP Morgan Chase Health Award in 2002 (San Jose, USA) and the Wilhelm Exner Medal 2002 (Vienna, Austria), the Karl-Heinz-Beckurts-Prize for 2000 (Munich, Germany), and the Young Investigator's Award of the German Industry Fund.
He has been an inventor on more than 25 patent families and is co-founder of four companies, Morphosys AG (recently acquired by Novartis), Molecular Partners AG (Zürich, Switzerland) and G7 Therapeutics (Zürich, Switzerland; merged with Heptares/Sosei [UK/Japan]) and Vector BioPharma.
His research in protein engineering has made important contributions to five areas
Website:
https://plueckthun.bioc.uzh.ch
The lecture will highlight designed binding proteins and concentrate on two application areas.
First, to enable in vivo production of therapeutic proteins, we have combined several protein engineering technologies to devise a new platform, termed SHielded, REtargeted ADenovirus (SHREAD). It is based on virus-like particles that are devoid of any viral genes, but contain 36 kb of DNA that can encode multiple genes and complex regulatory regions. To target particular cells and organs, an adapter strategy has been devised, based on the DARPin platform, to selectively target any surface receptor of interest. To hide the particles from the immune system and to minimize liver targeting, a protein shield was developed covering the particles.
In vivo applications have included expressing therapeutic anti-tumor antibodies, therapeutic cytokines or bispecific T-cell engagers in situ, as well as infecting and reprogramming T-cells in vivo, and targeting of dendritic cells in lymph nodes to co-express cytokines there for highly efficient tumor vaccination.
Second, we challenge the paradigm of selection from large universal libraries to obtain binding proteins rapidly and efficiently — and we also challenge the paradigm of individually de novo designing each binder for each target. When it comes to linear epitopes, we found it possible to exploit the periodicity of peptide bonds and create a completely modular system, based on a binding protein design that shares the same periodicity, using Armadillo Repeat Proteins.
Using orthogonal approaches of design, selection, evolution, biophysical testing, and structure determination, significant progress has been reached toward the creation of a system of modular binding proteins that are modular and complementary to a given peptide sequence. We believe that this technology can provide a new paradigm of creating binding proteins for many challenges in biomedical research.
Biography:
Andreas Plückthun has been Professor of Biochemistry at the University of Zürich, Switzerland since 1993. He studied chemistry at the University of Heidelberg (Germany). He received a PhD from the University of California at San Diego in 1982 (with Ed Dennis), was postdoctoral fellow at Harvard University (1982-85) (with Jeremy Knowles) and from 1985 until 1993, group leader at the Gene Center and Max-Planck-Institute for Biochemistry in Martinsried near Munich.
He has written over 500 publications, which have been cited over 50,000 times (h-index 130) [Google Scholar]. In 2003, he was elected to the German Academy of Science. In 1992, he was elected member of EMBO.
He received, among others, the 2016 Christian-Anfinsen Award of the Protein Society for "pioneering contributions to protein engineering", and the Swiss Technology Award 2005 (Bern, Switzerland) and the deVigier Award in 2005, the JP Morgan Chase Health Award in 2002 (San Jose, USA) and the Wilhelm Exner Medal 2002 (Vienna, Austria), the Karl-Heinz-Beckurts-Prize for 2000 (Munich, Germany), and the Young Investigator's Award of the German Industry Fund.
He has been an inventor on more than 25 patent families and is co-founder of four companies, Morphosys AG (recently acquired by Novartis), Molecular Partners AG (Zürich, Switzerland) and G7 Therapeutics (Zürich, Switzerland; merged with Heptares/Sosei [UK/Japan]) and Vector BioPharma.
His research in protein engineering has made important contributions to five areas
- Antibody engineering: he developed the first antibody expression in E. coli, the first fully synthetic antibody library and made many contributions to antibody stability and design
- Scaffold engineering: he developed the repeat proteins as alternative scaffolds, especially the DARPin technology, and the Armadillo technology
- Directed evolution: he developed ribosome display, the first truly in vitro protein evolution method
- GPCR engineering: he developed directed evolution methods for making G-protein coupled receptors stable for structural biology, drug design and screening.
- Targeted gene delivery: he developed a system of virus-like particles to deliver up to 36 kB DNA to selected cells in the body
Website:
https://plueckthun.bioc.uzh.ch
Practical information
- Informed public
- Free