A5048301589- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Transgenic Plants and Applications
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Medical Research and Treatments
- RNA and protein synthesis mechanisms
Boehringer Ingelheim (Germany)
2021-2022
BOKU University
2017-2021
Austrian Centre of Industrial Biotechnology (Austria)
2017-2021
In recent years, acceleration of development timelines has become a major focus within the biopharmaceutical industry to bring innovative therapies faster patients. However, in order address high unmet medical need even further potential be identified transform "speed-to-clinic" concepts into "warp-speed" programs. Recombinant Chinese hamster ovary (CHO) cell lines are predominant expression system for monoclonal antibodies (mAbs) and routinely generated by random transgene integration (RTI)...
Galactosylation as part of N-glycan processing is conducted by a set beta-1,4-galactosyltransferases (B4GALTs), with B4GALT1 the dominant isoenzyme for this reaction. Nevertheless, exact contributions key-player well other isoenzymes involved in N-glycosylation, B4GALT2, B4GALT3 and B4GALT4, have not been studied in-depth. To increase understanding protein- site-specific activities individual galactosyltransferases Chinese Hamster Ovary cells, panel triple deletion cell lines was generated...
Since the establishment of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9, powerful strategies for engineering CHO cell lines have emerged. Nevertheless, there is still room to expand scope CRISPR tool box further applications improve factories. Here, authors demonstrate activity alternative endonuclease Cpf1 in CHO-K1 first time and that it can be used parallel CRISPR/Cas9 without any interference. Both, Cas9 Cpf1, effectively multi-gene with a strategy based on...
MicroRNAs (miRNAs) are noncoding RNAs that serve as versatile molecular engineering tools to improve production cells by overexpression or knockdown of miRNAs showing beneficial adverse effects on cell‐culture performance. The genomic knockout (KO) in Chinese hamster ovary (CHO) has not been reported. However, given the significant number negative CHO‐bioprocess performance and development clustered regularly interspaced short palindromic repeats/CRISPR‐associated proteins (CRISPR/Cas9),...
With the emergence of new CRISPR/dCas9 tools that enable site specific modulation DNA methylation and histone modifications, more detailed investigations contribution epigenetic regulation to precise phenotype cells in culture, including recombinant production subclones, is now possible. These also allow a wide range applications metabolic engineering once impact such modifications on chromatin state available. In this study, enhanced were targeted viral promoter (CMV), an endogenous...
For the industrial production of recombinant proteins in mammalian cell lines, a high rate gene expression is desired. Therefore, strong viral promoters are commonly used. However, these have several drawbacks as they override cellular responses, not integrated into network, and thus can induce stress potentially epigenetic silencing. Endogenous advantage better response to state lower level by uncontrolled overexpression transgene. Such fine-tuning typically achieved endogenous enhancers...
Chinese hamster ovary (CHO) cells are the most widely used host for expression of therapeutic proteins. Recently, significant progress has been made due to advances in genome sequence and annotation quality unravel black box CHO. Nevertheless, many cases link between genotype phenotype context suspension cultivated production cell lines is still not fully understood. While frameshift approaches targeting coding genes frequently used, non-coding regions have received less attention with...
Chinese hamster ovary (CHO) cells are known not to express appreciable levels of the sialic acid residue N-glycolylneuraminic (NGNA) on monoclonal antibodies. However, we actually have identified a recombinant CHO cell line expressing an IgG with unusually high NGNA sialylation (>30%). Comprehensive multi-OMICs based experimental analyses unraveled root cause this atypical sialylation: (1) expression cytidine monophosphate-N-acetylneuraminic hydroxylase (CMAH) gene was spontaneously switched...