A5026293010- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Advanced NMR Techniques and Applications
- Viral gastroenteritis research and epidemiology
- NMR spectroscopy and applications
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Genomics and Phylogenetic Studies
- Genetics, Bioinformatics, and Biomedical Research
- Advanced MRI Techniques and Applications
- Transgenic Plants and Applications
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Receptor Mechanisms and Signaling
- T-cell and B-cell Immunology
- Electrochemical Analysis and Applications
- DNA and Nucleic Acid Chemistry
- Virus-based gene therapy research
AstraZeneca (United States)
2024
AstraZeneca (United Kingdom)
2019-2021
Melbourn Science Park
1999
University of Cambridge
1995-1998
Wilmington University
1993
HMG1 has two homologous, folded DNA-binding domains ("HMG boxes"), A and B, linked by a short basic region to an acidic C-terminal domain. Like the whole protein, which may perform architectural role in chromatin, individual boxes bind DNA without sequence specificity, have preference for distorted or prebent DNA, are able bend constrain negative superhelical turns. They show qualitatively similar properties with quantitative differences. We previously determined structure of HMG box from...
A large 1.29 x 10(11) antibody fragment library, based upon variable (V) genes isolated from human B-cells 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. Over 5000 target-specific antibodies were to the antigens with 3340 identified as modulating biological function (e.g. antagonism, agonism) target antigen. This represents an average approximately 120 functionally active per target. Analysis sample >800 unselected...
High‐mobility‐group protein 1 (HMG1) is a conserved chromosomal with two homologous DNA‐binding HMG‐box domains, A and B, linked by short basic region to an acidic carboxy‐terminal tail. NMR spectroscopy on the free didomain (AB) shows that HMG boxes do not interact. The has higher affinity for all DNA substrates tested than single domains significantly ability distort bending supercoiling. interaction of stabilized presence (≈20 residues, 9 which are Lys) links second box tail in intact...
Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool computation of haplotypes. Haplosaurus computes haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into Ensembl resource provides rapid and detailed retrieval. Using build database unique 1000 Genomes dataset reflecting real-world sequence variability their prevalence. For one in seven genes, common haplotype differs...
Despite the development of high-titer bioprocesses capable producing >10 g L−1 recombinant monoclonal antibody (MAb), some so called "difficult-to-express" (DTE) MAbs only reach much lower process titers. For widely utilized "platform" processes discrete variable is protein coding sequence product. However, there has been little systematic study to identify parameters that affect expression. This information vital, as it would allow us rationally design genetic and engineering strategies for...
The HMG-box sequence motif (approximately 80 residues) occurs in a number of abundant eukaryotic chromosomal proteins such as HMG1, which binds DNA without specificity, but with "structure specificity", well several sequence-specific transcription factors. HMG1 has two boxes, A and B, show approximately 30% identity, an acidic C-terminal tail. boxes are responsible for the ability protein to bend bind bent or distorted DNA. structure HMG box been determined by NMR spectroscopy B-domain [Weir...
High levels of protein expression are key to the successful development and manufacture a therapeutic antibody. Here, we describe two related antibodies, Ab001 Ab008, where shows markedly lower level relative Ab008 when stably expressed in Chinese hamster ovary cells. We use single-gene vectors structural analysis show that reduced titer is associated with VL CDR2 Ab001. adopted approaches improve First, used mutagenesis change single amino-acid residues back equivalent but this resulted...
Protein primary structure is a potential critical quality attribute for biotherapeutics. Identifying and characterizing any sequence variants present essential product development. A variant ~11 kDa larger than the expected IgG mass was observed by size-exclusion chromatography two-dimensional liquid coupled with online spectrometry. Further characterization indicated that 11 added to heavy chain (HC) Fc domain. Despite relatively large addition, only one unknown peptide detected mapping. To...
T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability eradicate cancer cells. Nevertheless, the widespread utility classical CD3-targeted TCEs has been limited by narrow index (TI) linked systemic CD4+ activation and aberrant cytokine release. One attractive approach circumvent pan CD3+ cells reduce risk release syndrome is redirect specific subsets A promising strategy use peptide-major histocompatibility I bispecific antibodies...
Recombinant DNA technology is widely used for different applications in biology, medicine and bio-technology. Viral transduction plasmid transfection are among the most frequently techniques to generate recombinant cell lines. Many of these methods result random integration into host genome. Rapid identification sites highly desirable order characterize engineered lines.We developed detectIS: a pipeline specifically designed identify genomic exogenous DNA, either containing one or more...