IIBR's multi-disciplinary protein engineering capabilities are supported by extensive professional expertise and a full complement of modern on-site facilities.
Innovative engineered proteins such as enzymes and antibodies or peptides are developed using the following capabilities:
Molecular design and engineering of novel proteins
- Construction of 3D models of macromolecular structures using homology modeling and simulation of molecular properties.
- Prediction of the effects of structural modifications on biological activity and physicochemical properties of the engineered products.
- Employment of site-directed mutagenesis and synthetic gene manipulation to engineer the properties predicted by structure-function analysis into the template sequences.
- Expression of the engineered proteins in optimized eukaryotic/bacterial systems.
- Functional analysis of the engineered protein based on a large plethora of analytical capabilities.
Engineering of recombinant antibodies
The antibody engineering R&D team at IIBR, is focused on the development of chimeric and fully humanized antibodies, with neutralizing capabilities towards bio-terror threat agents. The group's expertise ranges from classical approaches to state-of-the-art methodologies for the elucidation, characterization and engineering of antibodies.
These include:
- Development of functional, ELISA and BIAcore-based screens of monoclonal antibodies.
- Cloning of antibodies' variable regions, construction and expression of recombinant antibodies.
- Construction of naïve and immune libraries of phages displaying single-chain Fv (scFv).
- Epitope mapping of polyclonal and monoclonal antibodies by phage display random-peptide library screens.
- Efficacy and potency evaluation of candidate recombinant antibodies by in vitro and in vivo (pre-clinical) models.
- Production of candidate recombinant antibodies in eurokaryotic cells, cultivated in advanced.
bioreactor systems at IIBR’s cGMP production facility.
Optimization of physicochemical and pharmacokinetic properties of recombinant proteins
- Chemical modifications such as polyethylene-glycol (PEG) conjugation to improve the pharmacokinetic performance of recombinant proteins while preserving bioactivity and maximal homogeneity of the product.
- Tailoring of expressor cells for heterologous co-expression of specialized glycosyltransferases and glycosidases (e.g., sialyltransferase), to support production of glycoproteins displaying optimally processed oligosaccharides.
- Evaluation of recombinant product glycosylation by various methods, including mass spectrometric analysis, to ensure optimal processing and consistency of recombinant glycoprotein products.
Alteration of post-translation related traits such as state of assembly to transform the recombinant product into highly assembled oligomeric forms.
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Protein and Peptide Chemistry
Biologically active peptides are obtained through state-of-the-art solid phase synthesis and high resolution HPLC and solid phase synthesis. Multiple peptide synthesis, including construction of peptide libraries, is applied to establish structure-function relationships, and to generate tailored analogues or screen for immunogenic epitopes.
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