Aug. 1, 2011 Researchers have published the genomic sequence of the Chinese hamster ovary (CHO) K1 cell line online in the journal Nature Biotechnology. The CHO-K1 genome is the first published cell line genome decoded by de novo sequencing and assembly. The study yields a better understanding of the genetics of CHO cells and promises to accelerate the discovery and development of new recombinant protein therapies.
BGI, the world's largest genomics organization, and GT Life Sciences, Inc., a privately held biotechnology company that utilizes a proven metabolic modeling and experimental platform to drive the discovery and design of new products and processes for the life sciences field, collaborated on the study.
Chinese hamster ovary (CHO) cell lines are mammalian cells derived from the ovary of the Chinese hamster and are the preferred and most commonly used mammalian hosts today in biological and medical research. These cell lines play an important role in bioprocessing research and the development of therapeutic biopharmaceuticals. Currently the worldwide market for recombinant therapeutic proteins totals more than 99 billion USD in annual revenue from a broad range of products, including monoclonal antibodies, growth factors, hormones, and blood factors.
"Recognizing the importance of CHO cell lines, we and our partners jointly initiated a study of the genome sequence of CHO-K1 cells," said co-leading author of the study Xun Xu, Vice President of Research and Development at BGI and CEO BGI Americas. "The genome sequence and comprehensive annotation of the CHO-K1 cell line provides a useful and powerful tool for scientists in biomedical areas to optimize the production process and improve the yield of therapeutic proteins," he added.
GT Life Sciences' established business platform for metabolic modeling and engineering of mammalian cells has already proven effective in optimizing CHO cell media and developing novel selectable markers. With the advanced genome sequencing capability of BGI, the CHO-K1 ancestral cell line was sequenced by de novo sequencing and then assembled by BGI's Short Oligonucleotide Analysis Package, SOAPdenovo, resulting in the assembly of 2.45 Gb of the genomic sequence. This information was combined with transcriptome sequence data and led to the generation of 24,383 predicted genes.
"After working with cell culture for over 20 years, this is a dream come true," said Bernhard Palsson, Ph.D., co-founder of GT Life Sciences. "We can now hope to develop metabolic and cell line engineering procedures that approach those currently available for E. coli and yeast. This development signifies the start of genome-scale science for CHO."
"The CHO cell line genome revealed the secret of its protein synthesis, modification and viral resistance, which are very unique among other cell lines and make it the optimal protein production tool." said Xu. Because of the fact that differential glycosylation can substantially affect functional activity and immune responses, researchers carried out a genome-scale assessment of CHO-K1 genes involved in protein glycosylation pathways. They identified homologs to 99% of the human glycosylation-associated genes in the CHO-K1 genome, with 53% of them expressed. The high coverage of homologs provides a unique opportunity for glycoform manipulation in CHO cells. According to the report, the genome of CHO-K1 also provided insight into viral susceptibility genes and found that key genes associated with viral entry are not expressed in CHO-K1.
"Coupling the CHO sequence with a complete genome-scale model of CHO metabolism will prove highly productive in our ability to deliver next-generation process technologies for biopharmaceutical production in CHO and other mammalian cell lines," added Iman Famili, Ph.D., Sr. Director, Research and Development at GT Life Sciences.
"The CHO-K1 genome provides the foundation for studies of other CHO cell lines and is a major step forward in the application of genomics in the production of biopharmaceuticals," stated Dr. Jun Wang, Executive Director of BGI. "We expect that cell line engineering will be facilitated by genomics applications and the biopharmaceutical industry as well human healthcare will gain great benefits."
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- Xun Xu, Harish Nagarajan, Nathan E Lewis, Shengkai Pan, Zhiming Cai, Xin Liu, Wenbin Chen, Min Xie, Wenliang Wang, Stephanie Hammond, Mikael R Andersen, Norma Neff, Benedetto Passarelli, Winston Koh, H Christina Fan, Jianbin Wang, Yaoting Gui, Kelvin H Lee, Michael J Betenbaugh, Stephen R Quake, Iman Famili, Bernhard O Palsson, Jun Wang. The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1932
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