Chinese hamster ovary cell
Chinese hamster ovary (CHO) cells are a family of
History
Chinese hamsters had been used in research since 1919, where they were used in place of mice for typing
In 1948, the Chinese hamster was first used in the United States for breeding in research laboratories. In 1957, Theodore T. Puck obtained a female Chinese hamster from Dr. George Yerganian's laboratory at the Boston Cancer Research Foundation and used it to derive the original Chinese hamster ovary (CHO) cell line. Since then, CHO cells have been a cell line of choice because of their rapid growth in suspension culture and high protein production.[3][5]
The thrombolytic medication against myocardial infarction alteplase (Activase) was approved by the US Food and Drug Administration in 1987. It was the first commercially available recombinant protein produced from CHO cells.[3][6] CHO cells continue to be the most widely used manufacturing approach for recombinant protein therapeutics and prophylactic agents. [7][8] In 2018, 10 of the 15 highest selling drugs were made in CHO cells.[citation needed]
Properties
All CHO cell lines are deficient in proline synthesis.[9] Also, CHO cells do not express the epidermal growth factor receptor (EGFR), which makes them ideal in the investigation of various EGFR mutations.[10]
Furthermore, Chinese hamster ovary cells are able to produce proteins with complex glycosylations, post-translational modifications (PTMs) similar to those produced in humans. They are easily growable in large-scale cultures and have great viability, which is why they are ideal for GMP protein production. Also, CHO cells are tolerant to variations in parameters, be it oxygen levels, pH-value, temperature or cell density.[11]
Having a very low chromosome number (2n=22) for a mammal, the Chinese hamster is also a good model for radiation cytogenetics and tissue culture.[12]
Variants
Since the original CHO cell line was described in 1956, many variants of the cell line have been developed for various purposes.[9][additional citation(s) needed] In 1957, CHO-K1 was generated from a single clone of CHO cells.[13] According to an industry source, however, scientist Theodore Puck first isolated CHO-K1 in 1968.[1] Puck and colleagues reported starting a cell line of Chinese hamster ovarian origin in 1957.[14][15] Variants of K1 include the deposits in ATCC, ECACC, and a version adapted for growth in protein-free medium.[13]
CHO-K1 was mutagenized in the 1970s with
More recently, other selection systems have become popular and with vector systems that can more efficiently target active chromatin in CHO cells, antibiotic selection (puromycin) can be used as well to generate recombinant cells expressing proteins at high level. This sort of system requires no special mutation, so that non-DHFR-deficient host cell culture have been found to produce excellent levels of proteins.
Since CHO cells have a very high propensity of genetic instability (like all immortalised cells) one should not assume that the names applied indicate their usefulness for manufacturing purposes. For example, the three K1 offspring cultures available in 2013 each have significant accumulated mutations compared to each other.[13] Most, if not all industrially used CHO cell lines are now cultivated in animal component free media or in chemically defined media, and are used in large scale bioreactors under suspension culture.[9][13] The complex genetics of CHO cells and the issues concerning clonal derivation of cell population was extensively discussed.[18][19]
Genetic manipulation
Much of the genetic manipulation done in CHO cells is done in cells lacking
The CHO and CHO-K1 cell lines can be obtained from a number of biological resource centres such as the
Industrial use
CHO cells are the most common mammalian cell line used for mass production of therapeutic proteins such as monoclonal antibodies, used in 70% of therapeutic mAbs.
See also
References
- ^ a b c Eberle, Christian (3 May 2022). "CHO cells – 7 facts about the cell line derived from the ovary of the Chinese hamster". evitria. Retrieved 30 January 2024.
- ^ S2CID 20428452.
- ^ a b c "Vital Tools A Brief History of CHO Cells" (PDF). LSF Magazine. Winter 2015. pp. 38–47. Retrieved 5 April 2023.
- ISSN 1535-3702.
- ^ Fanelli, Alex (2016). "CHO Cells". Retrieved 28 November 2017.
- ISBN 9780080885049.
- PMID 34895638.
However, 70% of biologics, and almost all mAbs, are produced in Chinese hamster ovary (CHO) cells, as the most commonly used and preferred hosts for biopharmaceutical protein production.
- PMID 36741761.
Since 2016, about 70% of all rBPs and mAbs were produced from Chinese hamster ovary (CHO) cell lines
- ^ a b c d
Wurm FM; Hacker D (2011). "First CHO genome". Nature Biotechnology. 29 (8): 718–20. S2CID 8422581.
- PMID 19509222.
- ^ "CHO cells - 7 facts about the cell line derived from the ovary of the Chinese hamster". evitria AG. 3 May 2022.
- PMID 13563760.
- ^ a b c d
Lewis NE; Liu X; Li Y; Nagarajan H; Yerganian G; O'Brien E; et al. (2013). "Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome". Nature Biotechnology. 31 (8): 759–765. PMID 23873082.
- PMID 13598821.
- PMID 14294058.
- ^ a b
Urlaub G; Chasin LA (July 1980). "Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity". Proceedings of the National Academy of Sciences of the United States of America. 77 (7): 4216–4220. PMID 6933469.
- ^ a b
Urlaub G; Kas E; Carothers AD; Chasin LA (June 1983). "Deletion of the diploid dihydrofolate reductase locus from cultured mammalian cells". Cell. 33 (2): 405–412. PMID 6305508.
- .
- S2CID 13844297.
- ^
Lee F; Mulligan R; Berg P; Ringold G (19 November 1981). "Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids". Nature. 294 (5838): 228–232. S2CID 2501119.
- ^
Kaufman RJ; Sharp PA (25 August 1982). "Amplification and expression of sequences cotransfected with a modular dihydrofolate reductase complementary DNA gene". Journal of Molecular Biology. 159 (4): 601–621. PMID 6292436.
- ^ "General Cell Collection: CHO-K1". Hpacultures.org.uk. 2000-01-01. Retrieved 2013-05-21.
- PMID 24276168.
External links
- Chinese Hamster Genome Database
- Recombinant Protein Therapeutics from CHO Cells — 20 Years and Counting
- Puck TT, Cieciura SJ, Robinson A (December 1958). "Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects". J. Exp. Med. 108 (6): 945–56. PMID 13598821.
- Cellosaurus entry for CHO
- Cellosaurus entry for CHO-K1
- Cellosaurus entry for CHO-DG44
- Cellosaurus entry for CHO-DXB11