A5032615960- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- CRISPR and Genetic Engineering
- Protein purification and stability
- Transgenic Plants and Applications
- Radiopharmaceutical Chemistry and Applications
- Advanced Proteomics Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- 3D Printing in Biomedical Research
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Medical Imaging and Pathology Studies
- Cellular transport and secretion
- Microbial Inactivation Methods
- Bioinformatics and Genomic Networks
- Pancreatic function and diabetes
- Animal Virus Infections Studies
- Medical Imaging Techniques and Applications
- Lysosomal Storage Disorders Research
- Viral gastroenteritis research and epidemiology
- Advanced Biosensing Techniques and Applications
- Trypanosoma species research and implications
- Machine Learning in Bioinformatics
KTH Royal Institute of Technology
2014-2024
Wallenberg Wood Science Center
2019-2020
AlbaNova
2010-2019
Tampere University
2014
A database provides information on the relative abundances and locations of human proteins that are predicted to be secreted.
The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. human cell line HEK293 bio-synthetic potential human-like production attributes is currently used manufacturing of several therapeutic proteins viral vectors. Despite the popularity this strain we still have limited knowledge genetic composition its derivatives. Here present a genomic, transcriptomic metabolic gene analysis six most widely lines. Changes copy expression...
Background. Norovirus is a common cause of acute gastroenteritis in children. Serum immunoglobulin G (IgG) antibodies have been implicated protection against norovirus-associated gastroenteritis, but the level, specificity, and functionality necessary for remain to be elucidated. Methods. Norovirus-specific IgG genogroup II (GII)-4-2010 New Orleans (NO), GII-4-1999, GII-12-1998, GI-1-2001, GI-3-2002 virus-like particles (VLPs) were determined by enzyme-linked immunosorbent assay serum...
Emerging evidence suggests that the catalytically inactive ErbB3 (HER3) protein plays a fundamental role in normal tyrosine kinase receptor signaling as well aberrant functioning of these pathways, resulting several forms human cancers. has recently also been implicated resistance to ErbB2-targeting therapies. Here we report generation high-affinity ErbB3-specific Affibody molecules intended for future molecular imaging and biotherapeutic applications. Using high-complexity phage-displayed...
The HER3 receptor is implicated in the progression of various cancers as well resistance to several currently used drugs, and hence a potential target for development new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling pathways. aim this study was improve affinity binders hopefully increase inhibition efficacy enable high receptor-mediated uptake tumors. explored novel strategy maturation based on alanine scanning followed by design library...
Human embryonic kidney cells HEK293 can be used for the production of therapeutic glycoproteins requiring human post-translational modifications. High cell density perfusion processes are advantageous such but challenging due to shear sensitivity cells. To understand impact hollow filter separation devices, were cultured in bioreactors operated with tangential flow filtration (TFF) or alternating (ATF) at various rates. The average theoretical velocity profile these devices showed a lower...
Abstract Emerging strategies in cancer biotherapy include the generation and application of bispecific antibodies, targeting two tumor‐associated antigens for improved tumor selectivity potency. Here, an alternative format molecules was designed investigated, which Affibody were linked by albumin‐binding domain (ABD). are small (6 kDa) affinity proteins this new allows engineering with similar function as full‐length but a dramatically smaller size (around eight‐fold smaller). The ABD...
Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression human proteins through a systems biology analysis transcriptomes CHO and HEK293 during expression. In an comparison 24 express proteins, one third challenging displayed improved secretion upon host cell swapping from HEK293. Guided by comprehensive transcriptomics between lines,...
Recent studies have led to the recognition of epidermal growth factor receptor HER3 as a key player in cancer, and consequently this has gained increased interest target for cancer therapy. We previously generated several Affibody molecules with subnanomolar affinity receptor. Here, we investigate effects two these HER3-specific molecules, Z05416 Z05417, on different HER3-overexpressing cell lines. Using flow cytometry confocal microscopy, were shown bind three Furthermore, binding natural...
Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate metabolic characteristics associated with these limitations, we compare HEK293 clones producing either erythropoietin (EPO) (secretory) or GFP (non-secretory) at different rates. Transcriptomic functional analyses indicate significantly higher metabolism oxidative phosphorylation EPO producers compared parental cells. In addition, ribosomal genes...
Abstract The proteins secreted by human tissues (the secretome) are important for the basic understanding of biology, but also identification potential targets future diagnosis and therapy. Here, we present an annotation all predicted (n=2,623) with information about their spatial distribution in body. A high-throughput mammalian cell factory was established to create a resource recombinant full-length proteins. This used phenotypic assays involving β-cell dedifferentiation development...
Abstract The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. human cell line HEK293 bio-synthetic potential human-like production is today used manufacturing of several therapeutic proteins viral vectors. Despite this increasing popularity there still limited knowledge the detailed genetic composition derivatives strain. Here we present a genomic, transcriptomic metabolic gene analysis six most widely lines. Changes copy...
Aggregation of therapeutic bispecific antibodies negatively affects the yield, shelf-life, efficacy and safety these products. Pairs stable Chinese hamster ovary (CHO) cell lines produced two difficult-to-express with different levels aggregated product (10-75% aggregate) in a miniaturised bioreactor system. Here, transcriptome analysis was used to interpret biological causes for aggregation identify strategies improve yield quality. Differential expression- gene set revealed upregulated...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
Within the field of combinatorial protein engineering there is a great demand for robust high-throughput selection platforms that allow unbiased library display, affinity-based screening, and amplification selected clones. We have previously described development staphylococcal display system used displaying both alternative-scaffolds antibody-derived proteins. In this study, objective was to generate an improved expression vector screening high-complexity naïve affibody library, facilitate...
Abstract Mammalian cells are critical hosts for the production of most therapeutic proteins and many biomedical research. While cell line engineering bioprocess optimization have yielded high protein titers some recombinant proteins, remain difficult to express. Here, we decipher factors influencing yields in Chinese hamster ovary (CHO) as they produce 2165 different from human secretome. We demonstrate that variation within our panel cannot be explained by transgene mRNA abundance....
Rare diseases are, despite their name, collectively common and millions of people are affected daily conditions where treatment often is unavailable. Sulfatases a large family activating enzymes related to several these diseases. Heritable genetic variations in sulfatases may lead impaired activity reduced macromolecular breakdown within the lysosome, with severe lethal as consequence. While therapeutic options scarce, for some sulfatase deficiencies by recombinant enzyme replacement...
Abstract Precise epitope determination of therapeutic antibodies is great value as it allows for further comprehension mechanism action, responsiveness prediction, avoidance unwanted cross reactivity, and vaccine design. The golden standard discontinuous the laborious X-ray crystallography method. Here, we present a combinatorial method rapid mapping epitopes by mammalian antigen display, eliminating need protein expression purification. facilitated automated workflows tailored software...