A5090422381- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Respiratory viral infections research
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Biochemical and Structural Characterization
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Carbohydrate Chemistry and Synthesis
- Cytomegalovirus and herpesvirus research
- Virology and Viral Diseases
- Biosimilars and Bioanalytical Methods
- Reproductive System and Pregnancy
- Artificial Immune Systems Applications
- Fungal and yeast genetics research
- Diabetes and associated disorders
Biogen (Switzerland)
2021
Molecular Partners (Switzerland)
2007-2020
University of Zurich
1988-2015
Paul Scherrer Institute
2010
Federal Department of Home Affairs
2008
Walter Reist Holding (Switzerland)
2008
KTH Royal Institute of Technology
1992-2002
Center of Immunology Pierre Fabre
1992-1998
Université Claude Bernard Lyon 1
1993-1994
Pierre Fabre (France)
1994
Antigen-binding receptors on T lymphocytes and IgG antibodies with the same antigen-binding specificity as T-cell display shared or identical idiotypes. This was shown using a system where adult F1 hybrid rats between two inbred strains were inoculated from one parental strain. Such produce directed against idiotypic determinants present alloantibodies, produced in donor genotype strain for alloantigens of other The nature antialloantibody serum alloantibodies demonstrated both by indirect...
Ankyrin repeat (AR) proteins mediate innumerable protein-protein interactions in virtually all phyla. This finding suggested the use of AR as designed binding molecules. Based on sequence and structural analyses, we a consensus with fixed framework randomized interacting residues. We generated several combinatorial libraries consisting defined numbers this repeat. Randomly chosen library members are expressed soluble form cytoplasm Escherichia coli constituting up to 30% total cellular...
Slow-clearing, tumor-targeting proteins such as monoclonal antibodies typically exhibit high tumor accumulation but low tissue contrast, whereas intermediate-sized scFvs show faster clearance only moderate accumulation. For both, targeting does not seem to improve further above an optimal affinity. We here that with very small high-affinity designed ankyrin repeat (DARPins), these limits can be overcome. have systematically investigated the influence of molecular mass and affinity on DARPins...
Normal rat lymphocyte populations house a high percentage of lymphocytes with idiotypic, antigen‐binding receptors for the major histocompatibility complex antigens rat. These can be isolated from normal serum or supernatants. Idiotypic, molecules released Lewis were thus using anti‐(Lewis anti‐DA) immuno‐adsorbents. Analysis by SDS polyacrylamide elertrophoresis labeled external internal means ( 125 I 3 H) demonstrated that B produce ‘conventional’7S–8S IgM type. T‐lymphocyte‐derived had...
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage three units spike protein trimer SARS-CoV-2 and inhibit ACE2 binding high potency, as revealed by cryo-electron microscopy analysis. cooperative together...
Repeat proteins, such as ankyrin or leucine‐rich repeat are ubiquitous binding molecules, which occur, unlike antibodies, intra‐ and extracellularly. Their unique modular architecture features repeating structural units (repeats), stack together to form elongated domains displaying variable target‐binding surfaces. Based on this modularity, we developed a novel strategy generate combinatorial libraries of polypeptides with highly diversified specificities. This includes the consensus design...
A novel expression system for surface display of heterologous proteins on Staphylococcus carnosus cells has been developed. Taking advantage the promoter and secretion signals, including a propeptide region, from lipase gene hyicus cell wall-spanning membrane-binding region protein aureus, efficient an 80-amino-acid peptide malaria blood stage antigen could be achieved. serum albumin binding streptococcal G was used both as general reporter molecule to increase accessibility...
The specific intracellular inhibition of protein activity at the level allows determination function in cellular context. We demonstrate here use designed ankyrin repeat proteins as tailor-made kinase inhibitors. target was aminoglycoside phosphotransferase (3')-IIIa (APH), which mediates resistance to antibiotics pathogenic bacteria and shares structural homology with eukaryotic kinases. Combining a selection screening approach, we isolated 198 potential APH inhibitors from highly diverse...
Anti-idiotypic antibodies made against the antigen-binding receptors of T lymphocytes for a given antigen (Ag-B locus antigens in rats) can be shown to react with IgG same reactivity. Using such anti-idiotypic antibodies, normal Lewis B and type visualized by use anti-(Lewis-anti-DA) antibodies. Visualization was possible direct fluorescent antibody tests or autoradiography. first technique naked eye observations 6.2% expressed idiotypic markers signifying anti-DA reactivity, whereas...
Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens rat, Ag-B antigens. Such purified naturally occurring receptor molecules, they T- B-lymphocyte origin, used in a polymerized form provoke production auto-anti-idiotypic antibodies when injected back into rats. As consequence this autoimmunity, lymphocytes these depleted cells carrying relevant...
A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind albumin of different species with nanomolar affinities, and significantly improved pharmacokinetic properties both in mouse cynomolgus monkey compared to non-serum DARPin® In addition, they exhibit high thermal stability storage stability, which an essential feature their use drug development. Covalently linking a domain other...