Selection of high-producing CHO cells using NPT selection marker with reduced enzyme activity

Sautter, Kerstin; Enenkel, Barbara

doi:10.1002/bit.20374

Cited by 51Viral Infectious Diseases and Gene Expression in InsectsAnimal Genetics and ReproductionVirus-based gene therapy research

Selection of high-producing CHO cells using NPT selection marker with reduced enzyme activity

Sautter, Kerstin, Enenkel, Barbara·2005·Biotechnology and Bioengineering

DOI 10.1002/bit.20374

Open this paper in CoChat — free account

Abstract

We developed an expression system that aimed to increase the proportion of high producers in a transfected cell population in order to reduce the effort in clone screening. The principle is based on the impairment of the selection marker. Twelve single‐point mutations in more or less conserved domains of the resistance marker gene neomycin‐phosphotransferase (NPT) resulted in different degrees of reduced enzyme activity, depending on the amino acid conservation and the kind of amino acid exchange. In all transfected, mutant‐NPT bearing CHO‐DG44 cell pools surviving the selection with G418, the ratio of high‐producing cells to total cell number was higher than in pools selected with wildtype‐NPT. Furthermore, these pools showed, in comparison to wildtype‐NPT selected pools, not only higher NPT‐RNA levels but also increased specific productivities and higher titers of a coexpressed biopharmaceutically relevant product. Elevated productivity could be ascribed to higher gene copy numbers, integration into chromatin regions with higher transcriptional activity, or a combination of both effects. Thus, the use of NPT‐mutants as selection markers is suitable for the enrichment of high producers in a transfected CHO‐DG44 cell population, since cell survival is achieved only if the enzymatic impairment of the cointegrated resistance marker is compensated by a higher expression level. © 2005 Wiley Periodicals, Inc.

Integrity signals

Registry

Crossref · 10.1002/bit.20374

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

STAR elements were discovered by a genomic screen of elements that would increase transgene expression.
“They were discovered by a genomic screen of elements that would increase transgene expression.(Kwaks et al., 2003;Sautter and Enenkel, 2005;Hoeksema et al., 2011;Van Blokland et al., 2011;Harraghy et al., 2015).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Sautter and Enenkel, 2005

Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes
Shaw, K. J., Rather, P. N., Hare, R. S., & Miller, G. H. (1993) · Microbiological Reviews · doi:10.1128/mr.57.1.138-163.1993 · Cited by 1,195 · see citing works
Aminoglycosides: Activity and Resistance
Mingeot‐Leclercq, M., Glupczynski, Y., & Tulkens, P. M. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.4.727 · Cited by 1,105 · see citing works
Human monocyte chemoattractant protein‐1 (MCP‐1) Full‐length cDNA cloning, expression in mitogen‐stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE
Yoshimura, T., Yuhki, N., Moore, S. K., Appella, E., Lerman, M. I., & Leonard, E. J. (1989) · FEBS Letters · doi:10.1016/0014-5793(89)80590-3 · Cited by 589 · see citing works
Effect of gamma rays at the dihydrofolate reductase locus: Deletions and inversions
Urlaub, G., Mitchell, P. J., Käs, E., Chasin, L. A., Funanage, V. L., Myoda, T. T., & Hamlin, J. L. (1986) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01671941 · Cited by 222 · see citing works
A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure.
Yenofsky, R. L., Fine, M., & Pellow, J. W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.9.3435 · Cited by 171 · see citing works
Analysis of Biological Selections for High-Efficiency Gene Targeting
Hanson, K. D., & Sedivy, J. M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.1.45 · Cited by 83 · see citing works
RAMPAGE: Promoter Activity Profiling by Paired-End Sequencing of 5′-Complete cDNAs
Batut, P. J., & Gingeras, T. (2013) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb25b11s104 · Cited by 79 · see citing works
Nucleotide sequence of Acinetobacter baumannii aphA‐6 gene: evolutionary and functional implications of sequence homologies with nucleotide‐binding proteins, kinases and other aminoglycoside‐modifying enzymes
Martin, P., Jullien, E., & Courvalin, P. M. (1988) · Molecular Microbiology · doi:10.1111/j.1365-2958.1988.tb00070.x · Cited by 78 · see citing works
Dot assay for neomycin phosphotransferase activity in crude cell extracts
Platt, S. G., & Yang, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90429-5 · Cited by 67 · see citing works
Mutations in the aphA‐2 gene of transposon Tn5 mapping within the regions highly conserved in aminoglycoside‐phosphotransferases strongly reduce aminoglycoside resistance
Blázquez, J., DAVIES, J. E., & Moreno, F. (1991) · Molecular Microbiology · doi:10.1111/j.1365-2958.1991.tb00798.x · Cited by 23 · see citing works
A sensitive and simple assay for neomycin phosphotransferase II activity in transgenic tissue
Cabanes-Bastos, E., Day, A. G., & Lichtenstein, C. P. (1989) · Gene · doi:10.1016/0378-1119(89)90371-5 · Cited by 23 · see citing works
Altered substrate specificity by substitutions at Tyr218 in bacterial aminoglycoside 3′-phosphotransferase-II
Kocabıyık, S., & Perlin, M. H. (1992) · FEMS Microbiology Letters · doi:10.1016/0378-1097(92)90529-w · Cited by 18 · see citing works
Site-specific mutations of conserved C-terminal residues in aminoglycoside 3′-phosphotransferase II: Phenotypic and structural analysis of mutant enzymes
Kocabıyık, S., & Perlin, M. H. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91715-3 · Cited by 16 · see citing works
Determination of transient or stable neo expression levels in mammalian cells
Duch, M., Paludan, K., Pedersen, L., Jørgensen, P., Kjeldgaard, N. O., & Pedersen, F. S. (1990) · Gene · doi:10.1016/0378-1119(90)90373-y · Cited by 12 · see citing works

Flagged first, then by citations

Sorted by citations

Advances in Mammalian cell line development technologies for recombinant protein production
Lai, T., Yang, Y., & Ng, S. (2013) · Pharmaceuticals · doi:10.3390/ph6050579 · Cited by 322 · see citing works
Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Recent advances in mammalian protein production
Bandaranayake, A. D., & Almo, S. C. (2014) · FEBS Letters · doi:10.1016/j.febslet.2013.11.035 · Cited by 222 · see citing works
IRES-mediated Tricistronic vectors for enhancing generation of high monoclonal antibody expressing CHO cell lines
Ho, S. C. L., Bardor, M., Feng, H., Mariati, Tong, Y. W., Song, Z., Yap, M. G. S., & Yang, Y. (2011) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2011.09.023 · Cited by 148 · see citing works
Transcriptome and Proteome Profiling to Understanding the Biology of High Productivity CHO Cells
Nissom, P. M., Sanny, A., Kok, Y. J., Hiang, Y. T., Chuah, S. H., Tan, K. S., Lee, Y. Y., Wong, K. T. K., Hu, W., Sim, M. Y. G., et al. (2006) · Molecular Biotechnology · doi:10.1385/mb:34:2:125 · Cited by 120 · see citing works
Accelerated Clone Selection for Recombinant CHO Cells Using a FACS‐Based High‐Throughput Screen
DeMaria, C. T., Cairns, V. R., Schwarz, C., Zhang, J., Guerin, M., Zuena, E., Estes, S. D., & Karey, K. P. (2007) · Biotechnology Progress · doi:10.1021/bp060298i · Cited by 86 · see citing works
Development and Production of Commercial Therapeutic Monoclonal Antibodies in Mammalian Cell Expression Systems: An Overview of the Current Upstream Technologies
Chartrain, M. M., & Chu, L. (2008) · Current Pharmaceutical Biotechnology · doi:10.2174/138920108786786367 · Cited by 83 · see citing works
Generation of stable cell lines by site-specific integration of transgenes into engineered Chinese hamster ovary strains using an FLP-FRT system
Zhou, H., Liu, Z., Sun, Z., Huang, Y., & Yu, W. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.03.020 · Cited by 65 · see citing works
Impact of Using Different Promoters and Matrix Attachment Regions on Recombinant Protein Expression Level and Stability in Stably Transfected CHO Cells
Ho, S. C. L., Mariati, Yeo, J. H. M., Fang, S. G., & Yang, Y. (2014) · Molecular Biotechnology · doi:10.1007/s12033-014-9809-2 · Cited by 62 · see citing works
Heterologous expression of the lipid transfer protein CERT increases therapeutic protein productivity of mammalian cells
Florin, L., Pegel, A., Becker, E., Hausser, A., Olayioye, M. A., & Kaufmann, H. (2009) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2009.02.014 · Cited by 59 · see citing works
High‐throughput screening and selection of mammalian cells for enhanced protein production
Priola, J. J., Calzadilla, N., Baumann, M., Borth, N., Tate, C. G., & Betenbaugh, M. J. (2016) · Biotechnology Journal · doi:10.1002/biot.201500579 · Cited by 53 · see citing works
Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44
NG, S., Wang, D. I. C., & YAP, M. (2007) · Metabolic Engineering · doi:10.1016/j.ymben.2007.01.001 · Cited by 51 · see citing works
Screening Strategies for High-Yield Chinese Hamster Ovary Cell Clones
Yang, W., Zhang, J., Xiao, Y., Li, W., & Wang, T. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.858478 · Cited by 43 · see citing works
Generation of monoclonal antibody-producing mammalian cell lines
Ho, S. C., Tong, Y. W., & Yang, Y. (2013) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.13.8 · Cited by 42 · see citing works
A highly efficient modified human serum albumin signal peptide to secrete proteins in cells derived from different mammalian species
Attallah, C. V., Etcheverrigaray, M., Kratje, R. B., & Oggero, M. (2017) · Protein Expression and Purification · doi:10.1016/j.pep.2017.01.003 · Cited by 40 · see citing works
Engineering selection stringency on expression vector for the production of recombinant human alpha1-antitrypsin using Chinese Hamster ovary cells
Chin, C. L., Chin, H. K., Chin, C. S. H., Lai, E. T., & Ng, S. K. (2015) · BMC Biotechnology · doi:10.1186/s12896-015-0145-9 · Cited by 37 · see citing works
The use of glutamine synthetase as a selection marker: recent advances in Chinese hamster ovary cell line generation processes
Fan, L., Frye, C. C., & Racher, A. J. (2013) · Pharmaceutical Bioprocessing · doi:10.4155/pbp.13.56 · Cited by 35 · see citing works
Optimized Selection Marker and CHO Host Cell Combinations for Generating High Monoclonal Antibody Producing Cell Lines
Yeo, J. H. M., Ho, S. C. L., Mariati, M., Koh, E. Y. C., Tay, S. J., Woen, S., Zhang, P., & Yang, Y. (2017) · Biotechnology Journal · doi:10.1002/biot.201700175 · Cited by 34 · see citing works
Epigenetic regulatory elements: recent advances in understanding their mode of action and use for recombinant protein production in mammalian cells
Harraghy, N., Calabrese, D., Fisch, I., Girod, P., LeFourn, V., Regamey, A., & Mermod, N. (2015) · Biotechnology Journal · doi:10.1002/biot.201400649 · Cited by 32 · see citing works
A novel, high stringency selection system allows screening of few clones for high protein expression
VANBLOKLAND, H., Kwaks, T., Sewalt, R. G. A. B., Verhees, J., Klaren, V. N. A., Siersma, T. K., Korse, J. W. M., Teunissen, N. C., Botschuijver, S., & VANMER, C. (2006) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2006.09.023 · Cited by 25 · see citing works
Evaluating the use of a CpG free promoter for long-term recombinant protein expression stability in Chinese hamster ovary cells
Ho, S. C. L., Koh, E. Y. C., Soo, B. P. C., Mariati, Chao, S., & Yang, Y. (2016) · BMC Biotechnology · doi:10.1186/s12896-016-0300-y · Cited by 22 · see citing works
Utilization of non‐AUG initiation codons in a flow cytometric method for efficient selection of recombinant cell lines
Cairns, V. R., DeMaria, C. T., Poulin, F., Sancho, J., Liu, P., Zhang, J., Campos‐Rivera, J., Karey, K. P., & Estes, S. D. (2011) · Biotechnology and Bioengineering · doi:10.1002/bit.23219 · Cited by 18 · see citing works
Methods to create a stringent selection system for mammalian cell lines
Blokland, H. J. M. V., Hoeksema, F., Siep, M., Otte, A. P., & Verhees, J. (2011) · Cytotechnology · doi:10.1007/s10616-011-9354-9 · Cited by 16 · see citing works
Generation of High-Expressing Cells by Methotrexate Amplification of Destabilized Dihydrofolate Reductase Selection Marker
Ng, S. K. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-352-3_11 · Cited by 15 · see citing works
Weak promoters to drive selection marker expression: Improvement of cell line development process for therapeutic protein production in CHO-K1 cells
Grindes, L., Florimond, C., Ribault, S., Raymond, C., Dieryck, W., Joucla, G., & Corbin, C. (2023) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2023.05.001 · Cited by 14 · see citing works
Optimised mammalian expression through the coupling of codon adaptation with gene amplification: Maximum yields with minimum effort
Kotsopoulou, E., Bosteels, H., Chim, Y.-T., Pegman, P. M., Stephen, G. G., Thornhill, S. I., Faulkner, J. D., & Uden, M. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.02.004 · Cited by 12 · see citing works
Large Scale Suspension Culture of Mammalian Cells
Alldread, R. M., Birch, J. R., Metcalfe, H. K., Farid, S. S., Racher, A. J., Young, R. J., & Khan, M. (2014) · Wiley eBooks · doi:10.1002/9783527683321.ch12 · Cited by 9 · see citing works
Stabilizing and Anti-Repressor Elements Effectively Increases Transgene Expression in Transfected CHO Cells
Li, Q., Yan, R., Yang, Y. X., Mi, C., Jia, Y., & Wang, T. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.840600 · Cited by 6 · see citing works
Development and qualification of a high-yield recombinant human Erythropoietin biosimilarPreprint
Nag, K., Islam, M. J., Khan, M. M. R., Chowdhury, M. M. R., Sarker, M. E. H., Kumar, S., Khan, H., Chakraborty, S., Roy, R., Roy, R., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.22.525046 · Cited by 6 · see citing works
Development of Magoh protein‐overexpressing HEK cells for optimized therapeutic protein production
Mufarrege, E. F., Benizio, E., Prieto, C. C., Chiappini, F. A., Rodríguez, M. C., Etcheverrigaray, M., & Kratje, R. B. (2020) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1915 · Cited by 3 · see citing works
Development of an attenuated glutamine synthetase (GS) selection system for the stable expression of tissue plasminogen activator in CHO-K1 cells
Raigani, M., Namdar, P., Barkhordari, F., Seyedjavadi, S. S., Rahimpour, A., & Adeli, A. (2025) · Preparative Biochemistry & Biotechnology · doi:10.1080/10826068.2025.2454335 · Cited by 1 · see citing works
Antibody Expression from Bacteria to Transgenic Animals
Stephens, P. E., & Sweeney, B. (2011) · Modecular medicine and medicinal · doi:10.1142/9781848166295_0006 · Cited by 1 · see citing works
Recombinant protein expression in mammalian cells
Joshi, M., Verma, P., Mago, P., Agrawal, Y., Gunwal, I., Khurana, S., Tanwar, J., Yadav, U., & Yadav, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-98388-4.00008-3 · Cited by 1 · see citing works
Engineering selection stringency on expression vector for the production of recombinant human alpha1-antitrypsin using Chinese Hamster Ovary cells
Chin, C. L., Chin, H. K., Chin, C. S. H., Lai, E. T., & KongNg, S. (2015) · BMC Proceedings · doi:10.1186/1753-6561-9-s9-p10 · Cited by 1 · see citing works
Methotrexate gene amplification for development of erythropoietin with 2 additional N-link producing cell lines
Santoso, A., Wisnuwardhani, P. H., Kusumawati, A., Herawati, N., Rubiyana, Y., Septisetyani, E. P., & Nurainy, N. (2020) · IOP Conference Series Earth and Environmental Science · doi:10.1088/1755-1315/439/1/012006 · Cited by 1 · see citing works
Effects of viral promoters, the Woodchuck hepatitis post-transcriptional regulatory element, and weakened antibiotic resistance markers on transgene expression in Chinese hamster ovary cells
Wang, W., Guo, X. H., Chen, S., Wang, T., Wang, F., Qin, L., & Wang, Y. (2020) · Process Biochemistry · doi:10.1016/j.procbio.2020.04.005 · Cited by 1 · see citing works
Cell line development
(2012) · Elsevier eBooks · doi:10.1533/9781908818096.421 · Cited by 1 · see citing works
Arbeitsgebiete der Bioverfahrenstechnik
(2013) · doi:10.1002/9783527673834.ch2 · Cited by 1 · see citing works
References
(2012) · Elsevier eBooks · doi:10.1016/b978-1-907568-37-4.50029-4 · Cited by 1 · see citing works
A combinatorial engineering approach to increase the productivity of CHO cells, and proteomic analysis of cell culture supernatant
Becker, E. (2008) · OPUS Publication Server of the University of Stuttgart (University of Stuttgart) · doi:10.18419/opus-1784
Induzierbare Genexpression in humanen mesenchymalen Stammzellen
Drechsel, M. (2008) · doi:10.5282/edoc.8527
BI HEX™ – Platform for Fast Track Generation of High Producer Cell Lines Leading to High-Titer Processes for Production of Therapeutic Proteins from Mammalian Cells
Schulz, T. W., Schlatter, S., Kaufmann, H., Enenkel, B., Hoffmann, H., & Grammatikos, S. (2010) · Springer eBooks · doi:10.1007/978-90-481-3419-9_62
Self-citation
Cell Line Development for Biomanufacturing Processes
Gadgil, M., & Hu, W. (2017) · doi:10.1002/9783527800599.ch12
Omics Analysis and Cellular Engineering for the Overexpression of Membrane Proteins in Mammalian Cells
Priola, J. J. (2015)
Antibiotics and ELISA as a Hyphenated Technique for Screening High Production Cell Lines from Transfected HEK293 Cells for the Production of Recombinant Follicle Stimulating Hormone
Hu, J., Liu, M., Han, J., & Zeng, B. (2017) · International Conference on Biomedical and Biological Engineering (BBE) · doi:10.2991/bbe-17.2017.2
Advances in Production of Therapeutic Monoclonal Antibodies
Mahajan, R. V., Chand, S., Singh, M. P., Kestwal, A., & Singh, S. (2019) · Wiley eBooks · doi:10.1002/9781119460053.ch7
Recombinant expression systems
(2015) · CRC Press eBooks · doi:10.1201/b19077-7
Mapeamento de regiões cromossômicas com alto potencial de expressão gênica como alvo para seu uso na produção de proteínas recombinantes
Pomatay, L. A. Q. (2020) · doi:10.11606/d.87.2020.tde-21092023-085334
Selection of high yield recombinant human bone morphogenetic protein 2 (rhBMP2) cell pool based on different screening markers used for CHO cell line development
Mirfeizollahi, A., & Kaghazian, H. (2025) · Journal of Cellular Biotechnology · doi:10.1177/23523689251359487
CHO endogenous weak promoters facilitating the development of high-yield cell lines
Tian, Y., Zhou, Y., Xiao, Z.-Y., Zhao, L., Ye, Q., & Tan, W.-S. (2026) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2026.05.005
The historical evolution of CHO cell line development for biologics production: 60 years and still counting.
Fieder, J., Schneider, S., & Fischer, S. (2026) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2026.2738418

Weak promoters to drive selection marker expression: Improvement of cell line development process for therapeutic protein production in CHO-K1 cells
Grindes, L., Florimond, C., Ribault, S., Raymond, C., Dieryck, W., Joucla, G., & Corbin, C. (2023) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2023.05.001 · Cited by 14 · see citing works
Effects of viral promoters, the Woodchuck hepatitis post-transcriptional regulatory element, and weakened antibiotic resistance markers on transgene expression in Chinese hamster ovary cells
Wang, W., Guo, X. H., Chen, S., Wang, T., Wang, F., Qin, L., & Wang, Y. (2020) · Process Biochemistry · doi:10.1016/j.procbio.2020.04.005 · Cited by 1 · see citing works
Gentechnische Verfahren zur Erzeugung und Selektion von hochproduzierenden CHO-Zellen
Sautter, K. (2003)
Self-citation
Development of a novel expression system for the production of recombinant proteins in Chinese hamster ovary cells based on the selection with a metabolic enzyme
Schüler, A. (2013) · Digitale Bibliothek Braunschweig (Verbundzentrale Göttingen (VZG)) · doi:10.24355/dbbs.084-201305160953-0
Attenuated glutamine synthetase as a selection marker in CHO cells to efficiently isolate highly productive stable cells for the production of antibodies and other biologics
Lin, P.-C., Chan, K. F., Kieß, I. A., Tan, J. L., Shahreel, W., Wong, S.-Y., & Song, Z. (2019) · mAbs · doi:10.1080/19420862.2019.1612690 · Cited by 42 · see citing works

Authors: Sautter, K., & Enenkel, B.
Affiliations: Boehringer Ingelheim (Germany) (DE)
Corresponding author: Enenkel, Barbara
Venue: Biotechnology and Bioengineering
Publisher: Wiley
Published: 2005-01-24
Volume: 89
Issue: 5
Pages: 530-538
ISSN: 0006-3592 (ISSN-L)
1097-0290
DOI: 10.1002/bit.20374
OpenAlex: W2029545026
Cited by: 51
References: 14
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2020: 4 · 2019: 1 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 5 · 2012: 2
FWCI: 0.87
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Biotechnology and Bioengineering (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords: neomycin phosphotransferase, reduced enzyme activity, G418 selection, CHO DG44 cells, clone screening, recombinant protein expression, gene copy number, transcriptional activity, point mutations, biopharmaceutical products
MeSH terms: Amino Acid Sequence, Animals, Antibodies, Monoclonal, Cell Survival, Clone Cells, Cricetulus, Genetic Markers, Gentamicins, Cricetinae, Molecular Sequence Data, Recombinant Proteins, Selection, Genetic, Transfection, Gene Expression, CHO Cells, Point Mutation, Protein Structure, Tertiary, Chemokine CCL2, Kanamycin Kinase, Amino Acid Motifs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Selection of high-producing CHO cells using NPT selection marker with reduced enzyme activity

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks