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Chinese hamster ovary (CHO) cells are a cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of therapeutic proteins.[1] They were introduced in the 1960s, are grown as a cultured monolayer and require the amino acid proline in their culture medium.

CHO cells are used in studies of genetics, toxicity screening, nutrition and gene expression, particularly to express recombinant proteins. Today, CHO cells are the most commonly used mammalian hosts for industrial production of recombinant protein therapeutics.

History[edit]

The use of the Chinese hamster in research began in 1919 where they were used in place of mice for typing pneumococci. They were subsequently found to be excellent vectors for transmission of kala-azar (a.k.a. visceral leishmaniasis), facilitating research in epidemiology.

In 1948, the Chinese hamster was brought to the United States for breeding in research laboratories. In the following years, the Chinese hamster became noteworthy for the cell lines that were derived from its tissues. Having a very low chromosome number (2n=22) for a mammal, the Chinese hamster is an ideal model for radiation cytogenetics and tissue culture.[2]

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 and high protein production. They have become the mammalian equivalent of Escherichia coli in research and biotechnology today, especially when long-term, stable gene expression and high yields of proteins are required.

Properties[edit]

CHO cells do not express the Epidermal growth factor receptor (EGFR), which makes them ideal in the investigation of various EGFR mutations.[3]

The first CHO cell line was derived from the original cell lines in Dr. Puck's laboratory through single cell cloning in 1957.[4] CHO-K1 was later derived from this ancestral cell line,[5] and it contains a slightly lower amount of DNA than the original CHO. CHO-K1 was mutagenized to generate CHO-DXB11 (also referred to as CHO-DUKX), a cell line lacking DHFR activity.[6] These cells have a deletion of one DHFR allele and a Missense mutation in the other. Subsequently, the proline-dependent CHO-pro3- strain, another derivative of the original CHO cell line, was mutagenized to yield CHO-DG44, a cell line with deletions of both DHFR alleles.[7] These two DHFR-minus strains require glycine, hypoxanthine, and thymidine (GHT) for growth. Although not initially intended for recombinant protein manufacture, DHFR-minus CHO cells were used for a number of pioneering experiments demonstrating stable transfection with an exogenous DHFR gene via selection in GHT-minus medium.[8] This genetic selection scheme remains one of the standard methods to establish stably transfected CHO cell lines for the production of recombinant therapeutic proteins. The multistep process begins with the molecular cloning of the gene of interest (GOI) and the dhfr gene in a single or in separate mammalian expression vectors. The plasmid DNA(s) carrying the two genes are then delivered into cells by transfection, and the cells are grown under selective conditions in GHT-minus medium. Each surviving cell will have one or more copies of the exogenous DHFR gene, usually along with the GOI, integrated in its genome.[9] The integrated plasmid copy number varies widely from one recombinant cell to another, but there is almost always only one integration site per cell even if multiple plasmids are transfected.[10] The growth rate and the level of recombinant protein production of each cell line also vary widely. To obtain a few stably transfected cell lines with the desired phenotypic characteristics, it may be necessary to evaluate several hundred candidate cell lines.

The CHO and CHO-K1 cell lines can be obtained from a number of biological resource centres such as the European Collection of Cell Cultures (ECACC) which is part of the Health Protection Agency Culture Collections. CHO-K1[11] data, such as growth curves, timelapse videos of growth, images and subculture routine information are available from ECACC.

See also[edit]

References[edit]

  1. ^ Jayapal K. P., Wlaschin K. F., Yap M. G. S., Hu W-S., (2007). "Recombinant protein therapeutics from CHO cells — 20 years and counting." (PDF). Chem. Eng. Prog. 103 (10): 40–47. 
  2. ^ Tjio J. H., Puck T. T., (1958). "Genetics of somatic mammalian cells. II. chromosomal constitution of cells in tissue culture.". J. Exp. Med. 108: 259–271. doi:10.1084/jem.108.2.259. PMC 2136870. PMID 13563760. 
  3. ^ Ahsan, A., S. M. Hiniker, M. A. Davis, T. S. Lawrence, and M. K. Nyati. "Role of Cell Cycle in Epidermal Growth Factor Receptor Inhibitor-Mediated Radiosensitization." Cancer Research 69.12 (2009): 5108-114. Print.
  4. ^ Wurm FM, Hacker D. "First CHO genome." Nat Biotechnol 2011;29(8):718–20.
  5. ^ Lewis, NE, et al. "Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome." Nat Biotechnol 31, 759–765 (2013). doi: 10.1038/nbt.2624
  6. ^ (Urlaub and Chasin, 1980)
  7. ^ (Urlaub et al., 1983)
  8. ^ (Ringold et al., 1981; Kaufman and Sharp, 1982; Scahill et al., 1983)
  9. ^ (Ringold et al., 1981; Kaufman and Sharp, 1982; Scahill et al., 1983)
  10. ^ (Wurm 1990)
  11. ^ "General Cell Collection: CHO-K1". Hpacultures.org.uk. 2000-01-01. Retrieved 2013-05-21. 

External links[edit]


Original courtesy of Wikipedia: http://en.wikipedia.org/wiki/Chinese_hamster_ovary_cell — Please support Wikipedia.
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58 videos foundNext > 

The Hamster: An Unexpected Journey Into Drug Manufacturing

An Ignite talk at Sheffield University on the history of the Chinese Hamster Ovary (CHO) cell line and a brief overview on manufacturing recombinant proteins.

ZEISS ELYRA: 3D superresolution imaging of Chinese Hamster Ovary (CHO) cells

CHO cells (Chinese Hamster Ovary cells), CEP152 (centriolar protein) (secondary antibody system conjugated to Alexa 647), 10 ms / frame. Courtesy of T. Klein, ...

CHO Cell Subculturing Demo

CHO Cell Cloning Procedure: Semi-Solid Cloning with ClonaCell™-CHO

For more information: http://www.stemcell.com/en/Products/Cell-type/CHO.aspx Cloning CHO cells using semi-solid cell culture media is an efficient cell line ...

Pro-Active CHO Cell Line Development for Bioproduction

After over 25 years of using CHO cells for the production of biotherapeutics, the majority of production gains have come through improvement to medias and feeds. Conversely, the potential for...

B&B: Construction of BAC-based physical map & analysis of chromosome rearrangement in CHO cell lines

Video Abstract from author Takeshi Omasa on his recently published B&B paper entitled "Construction of BAC-based physical map and analysis of chromosome ...

Life of Cells - The Robust Type

Learn more at: http://www.lifetechnologies.com/lifeofcells Think about it, we treasure our cells. They are precious. We are completely dependent on their health ...

High-Content Screening and Analysis in Cell-Based Assays for Drug Toxicity and Genotoxicity Testing

High-content analysis (HCA) and high-content screening (HCS) enable imaging of large numbers of cellular samples for a variety of life science applications.

Horizon Discovery lands a share of £1.67m Biotech research grant

The CEO of AIM listed Biotech research group Horizon Discovery (LON:HZD) tells Proactiveinvestors about their latest joint venture Genomics project.

Software-aided automatic laser optoporation and transfection of cells

Software-aided automatic laser optoporation and transfection of cells. Hans Georg Breunig et al (2015), Scientific Reports http://dx.doi.org/10.1038/srep11185 ...

58 videos foundNext > 

24 news items

 
BioPharma-Reporter.com
Tue, 09 Dec 2014 00:48:41 -0800

Horizon Discovery Group announced Monday that its bioproduction division has shipped its first commercially available engineered CHO (Chinese Hamster Ovary) cell line for use in manufacturing of antibodies.
 
StreetInsider.com
Mon, 08 Jun 2015 05:33:45 -0700

... and enhance the therapeutic effectiveness of certain antibodies, including a specific case study that resulted in superior performance of an antibody made in plants when compared directly to its CHO (Chinese Hamster Ovary Cell) produced counterpart.
 
Australian Life Scientist
Mon, 16 Feb 2015 20:07:30 -0800

South Australia's Medvet Science has licensed a cell line from ACYTE Biotech to produce its monoclonal cancer antibody APOMAB. Medvet has arranged to use ACYTE's XL-99 Chinese hamster ovary cell line to produce APOMAB in the quantities potentially ...
 
Mondaq News Alerts (registration)
Tue, 10 Mar 2015 05:36:57 -0700

The PTAB found that a person of ordinary skill would have been motivated to make this combination and that the claimed methods employing GAA "produced in chinese hamster ovary cell cultures" were obvious. The Myozyme® patents are just three of a ...

OutSourcing-Pharma.com

OutSourcing-Pharma.com
Mon, 02 Feb 2015 07:39:56 -0800

Contract research organization (CRO) Horizon has been selected as a “core facility” for supplying biopharma research tools to academic group the Tri-Institutional Therapeutics Discovery Institute.

BioPharma-Reporter.com

BioPharma-Reporter.com
Tue, 24 Jun 2014 07:09:55 -0700

The trick will ultimately be [showing] that you can confer in the CHO [Chinese hamster ovary] cell lines, but you can't change anything else [such as] sugars.” 'Two-pronged' attack. Commonly, viruses can enter cell culture raw materials from mice ...
 
BioPharma-Reporter.com
Tue, 20 May 2014 07:06:23 -0700

The equipment is being used for clone selection programmes to determine which CHO(Chinese hamster ovary) cell lines are stable and produce the highest titre mAbs. Gallus is also using Ambr15 for media selection and feed strategies for these mAbs during ...
 
GenomeWeb
Tue, 24 Jul 2012 12:05:30 -0700

The same chip was used to isolate and amplify individual chromosomes as part of a Chinese hamster ovary cell genome sequencing study published in Nature Biotechnology last year, while another similar chip was employed in a single-cell haplotyping ...
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