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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 E. 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.". 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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53 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 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 ...

Production Of Therapeutic Glycoproteins : Competitor and Patent Landscape Report

About the Report: The majority of clinically approved protein drugs bear some form of post-translational modification, most commonly glycosylation. Glycosyla...

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. ...

Jack, the Hamster

These animals grow to between 82 and 127 mm in body length (tail length 20–33 mm) and weigh 1.7 grams at birth, then as they get older can weigh 30–45 grams. They live two to three years...

Why Girls Are Entering Puberty Earlier Than Ever

DNews Audience Survey http://dne.ws/1dLMDtq Girls entering puberty earlier than usual is a problem first spotted nearly two decades ago. But the problem is s...

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 rear...

Remicade (infliximab) first time using Remicade Infusion

first time using Remicade Infusion, Remicade uses human and mouse proteins to create a chimeric monoclonal antibody. Enbrel is derived by introducing human D...

Fluorescence Imaging of Eukaryotic Endoplasmic Reticulum

This video shows a brief, real time stream of a live Chinese hamster ovary (CHO) cell treated with a special fluorescent dye known as a squaraine rotaxane. T...

53 videos foundNext > 

22 news items

 
JAMA: The Journal of the American Medical Association
Sun, 16 Nov 2014 08:07:30 -0800

... antibody).2 Accordingly, distinct manufacturing and purification processes are required for the 2 molecules (Fab in an Escherichia coli vector vs full-length antibody in a Chinese hamster ovary cell line), further underscoring each molecule's ...

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 ...
 
Insurance News Net
Wed, 09 Jul 2014 07:35:49 -0700

2013) Standard guide for performance of the Chinese hamster ovary cell/hypoxanthine guanine phosphoribosyl transferase gene mutation assay 2-141 ASTM F1984-99 (Reapproved Reaffirmation. 2013) Standard practice for testing for whole complement ...
 
Seeking Alpha
Mon, 17 Dec 2012 13:04:48 -0800

Enzyme replacement therapy ERT, the current primary treatment for Fabry disease provides patients with a recombinant form of human α-Gal A (generated by expressing gene encoding the enzyme in CHO Chinese hamster ovary cell lines), via intravenous ...
 
Chicago Tribune
Sun, 05 Feb 2012 14:29:33 -0800

... but we wanted people who had tenacity and determination, a refusal to fail." Although Strozier doubted she had the proper training or the ability to be "a real scientist," she tried it anyway and wound up working in a lab caring for a Chinese ...
 
News-Medical.net
Wed, 12 Dec 2012 22:13:54 -0800

The FDA placed a clinical hold on IB1001 in July 2012 when a number of study subjects developed antibodies to the host cell protein, Chinese Hamster Ovary cell proteins (CHOP), of IB1001. No clinical sequelae were associated with these antibodies and ...
 
Business Wire (press release)
Wed, 12 Dec 2012 16:18:07 -0800

The FDA placed a clinical hold on IB1001 in July 2012 when a number of study subjects developed antibodies to the host cell protein, Chinese Hamster Ovary cell proteins (CHOP), of IB1001. No clinical sequelae were associated with these antibodies and ...
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