A5086999133- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Advanced biosensing and bioanalysis techniques
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Bacteriophages and microbial interactions
- Blood groups and transfusion
- Immunotherapy and Immune Responses
- DNA and Nucleic Acid Chemistry
- SARS-CoV-2 and COVID-19 Research
- Prenatal Screening and Diagnostics
- Supramolecular Self-Assembly in Materials
- Mitochondrial Function and Pathology
- Chronic Lymphocytic Leukemia Research
- Microtubule and mitosis dynamics
- Renal and related cancers
- Cancer Immunotherapy and Biomarkers
- Nanofabrication and Lithography Techniques
- Biotin and Related Studies
- Modular Robots and Swarm Intelligence
- Genetics, Aging, and Longevity in Model Organisms
- T-cell and B-cell Immunology
- HER2/EGFR in Cancer Research
- Protein purification and stability
Aarhus University
2013-2023
Central Denmark Region
2023
Abstract Fc-less bispecific T-cell engagers have reached the immuno-oncology market but necessitate continual infusion due to rapid clearance from circulation. This work introduces a programmable serum half-life extension platform based on fusion of human albumin sequences engineered with either null (NB), wild type (WT) or high binding (HB) FcRn affinity combined engager. We demonstrate in humanised FcRn/albumin double transgenic mouse model (AlbuMus) ability tune sequence fused BiTE-like...
Abstract The compaction and organization of genomic DNA is a central mechanism in eukaryotic cells, but engineered architectural control over double‐stranded (dsDNA) notably challenging. Here, long dsDNA templates are folded into designed shapes via triplex‐mediated self‐assembly. Triplex‐forming oligonucleotides (TFOs) bind purines normal or reverse Hoogsteen interactions. In the triplex origami methodology, these non‐canonical interactions programmed to compact (linear plasmid)...
Today a number of synthetic antibody libraries different formats have been created and used for the selection large recombinant antibodies. One determining factors successful isolation antibodies from lies in quality i.e. correctly folded, functional contained library. Here, we describe construction novel, high quality, single domain library dubbed Predator. The is based on HEL4 with addition recently reported mutations concerning amino acid composition at positions critical folding...
Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies (mAbs) has shown anti-tumor activity in human trials, but can be associated with significant off-tumor toxicities involving FcγR interactions. Here, we introduce albumin-fused mouse and bispecific clinically favorable pharmacokinetics designed to confine 4-1BB costimulation the tumor microenvironment. These Fc-free agonists consist an EGFR-specific VHH antibody, a 4-1BB-specific scFv, albumin sequence...
Abstract With the advent of modern technologies enabling single cell analysis, it has become clear that small sub‐populations cells or even can drive phenotypic appearance tissue, both diseased and normal. Nucleic acid based allowing analysis been faster to mature, while aimed at analysing proteome a level is still lacking behind, especially which allow in tissue. Introducing methods, allows such will pave way for discovering new biomarkers with more clinical relevance, as these may be...
Abstract Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content apoptotic causing damage to surrounding cells, are quickly cleared engulfment. Tight regulation apoptosis engulfment is needed several pathologies such as cancer, neurodegenerative autoimmune diseases. There increasing evidence that machinery can regulate execution apoptosis. However, underlying molecular mechanisms poorly understood....
Expression of recombinant proteins often takes advantage peptide tags expressed in fusion to allow easy detection and purification the proteins. However, as peptides most are flexible appendages at N- or C-terminal, proteolytic cleavage may result removal tag sequence. Here, we evaluated functionality stability 14 different combinations commonly used for antibody fragments. The sequences were inserted with c-terminal end a domain based on HEL4 scaffold phagemid vector. This particular...
Abstract One of the hallmarks cancer is sustained angiogenesis. Here, normal endothelial cells are activated, and their formation new blood vessels leads to continued tumour growth. An improved patient condition often observed when angiogenesis prevented or normalized through targeting these genomically stable cells. However, intracellular targets constitute a challenge in therapy, as agents modulating have be delivered internalized specifically Selection antibodies binding certain cell...
Cancer immunotherapies such as bispecific T-cell engagers have seen limited adoption in prostate cancer (PC), possibly due to differing levels of receptor expression and effector infiltration between patients inherent defects engager design.CD8+ PSMA were determined by RNA sequencing primary PC tissue samples from 126 with localised 17 metastatic PC. Prognostic value was assessed through clinical parameters, including CAPRA-S risk score. A panel albumin-fused anti-CD3 × anti-PSMA different...
ABSTRACT Objective Cells of foetal origin circulating in the maternal peripheral bloodstream present a unique source for non‐invasive prenatal diagnostics. The aims this study were to raise antibodies against identified cells from blood, test properties these and determine cell type recognised by antibodies. Method male foetus blood sample FISH analysis X‐ Y‐ chromosomes. subjected phage display selection using novel single strategy. Selected tested immunocytochemistry on adult tissue...
There is a growing appreciation of single cell technologies to provide increased biological insight and allow development improved therapeutics. The central dogma explains why further advanced in studies targeting nucleic acids compared proteins, as acid amplification makes experimental detection possible. Here we describe novel method for round phage display selection antibody fragments from genetic libraries antigens expressed by rare cells tissue sections. We present discuss the results...
The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. application soluble angiotensin converting enzyme (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by short plasma half-life. This work presents recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the half-life an FcRn-driven cellular...
DNA Nanotechnology nanotechnology, so far, has almost exclusively relied on Watson–Crick base pairing. In article number 2302497, Minke A. D. Nijenhuis, Kurt V. Gothelf, and co-workers introduce a triplex origami methodology. They demonstrate that DNA, formed by Hoogsteen interactions, also possesses remarkable potential for nanoscale engineering. Triplex enables unprecedented large-scale architectural control over double-stranded templates, folding compacting them into sheets, bundles, even...
The folding of double-stranded DNA around histones is a central mechanism in eukaryotic cells for compacting the genetic information into chromosomes. Very few artificial methods are available controlling shape dsDNA at any level, whereas several have been developed to efficiently organize single-stranded and RNA variety well-defined nanostructures by programmed self-assembly , . Here, we show how long sequences can be spatially organized triplex forming oligonucleotides (TFOs), which bridge...
Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it challenging undertaking typically relies on recombinant site-specific conjugations. The scope utility this nature-inspired methodology would be broadened tremendously by the advent facile, scalable techniques glycosylation, which are currently missing. In work, we investigated one-pot aqueous protocol to achieve indiscriminate, surface-wide surface accessible amines (lysines...
The folding of double-stranded DNA around histones is a central mechanism in eukaryotic cells for compacting the genetic information into chromosomes. Very few artificial methods are available controlling shape dsDNA at any level, whereas several have been developed to efficiently organize single-stranded and RNA variety well-defined nanostructures by programmed self-assembly. Here, we show how long sequences can be spatially organized triplex-forming oligonucleotides (TFOs), which bridge...