The 5,000 human protein club

OriGene Technologies, Institute for Systems Biology to create standard database for 5,000 human proteins

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SEATTLE—OriGene Technologies Inc. and the Institute for Systems Biology (ISB) have a magic number: 5,000.

The parties recently announced they will create a proteotypic PeptideAtlas and SRM/MRM mass spectrometry standard database for 5,000 human proteins to enable quantitative protein analysis and facilitate lab-to-lab data validation. Under the companies' agreement, announced in June, OriGene will supply all 5,000 full-length human proteins to ISB for analysis in mass spectrometry. The companies will create a proteotypic PeptideAtlas and develop a single reaction monitoring, multiple reaction monitoring (SRM/MRM) mass spectrometry standard database for the proteins.

Proteomics research and biomarker development hold great promise in personalized medicine. Mass spectrometry, especially SRM/MRM, has emerged as a new platform for simultaneous quantitative characterization of multiple proteins, thus making it an ideal choice for high-throughput proteomics and clinical biomarker research. SRM/MRM is widely used for biomarker identification and quantification, especially when there is no suitable ELISA pair for targets under investigation. As the protein project is completed, the information will be made available for further research, with many dimensions of human proteins to be studied beyond identification and modification.

With headquarters in Rockville, Md., OriGene Technologies is a gene-centric life sciences tool company dedicated to support academic, pharmaceutical and biotech companies in their research of gene functions and drug discovery. James K. Hu, vice president of corporate development at OriGene Technologies, notes that OriGene has produced more than 12,000 transient transfected over-expression lysates and more than 5,000 purified human proteins made in human HEK293 cells. Hu says he believes "by having a SRM/MRM mass spectrometry standard available for researchers, it would increase the velocity of biomarker discovery using mass spec instruments."

"At the completion of the project, this database will be made available to all researchers who can easily find the top three to six experiment-derived peptide sequences for each of the 5,000 human proteins, and apply them in quantitative proteomics analysis through SRM/MRM mass spectrometry," Hu says.

He says it was an easy decision to enter into the collaboration with ISB.

"The Institute for Systems Biology and its co-founders, Drs. Ruedi Aebersold and Leroy Hood, are recognized leaders in the study of systems biology, a new kind of personalized medicine research that can tackle the multi-disciplinary challenges integrating many sciences including biology, chemistry, physics, computation, mathematics and medicine," Hu says. "Of particular significance to this collaboration is the leadership position and contribution to proteomics research made by Aebersold, Hood and Dr. Moritz on development of quantitative analytical protein chemistry and proteomic techniques on mass spectrometry for the purpose of profiling cellular proteins and biomarkers in cancer and infectious diseases."

Based in Seattle, the ISB is a nonprofit research institute dedicated to the study and application of systems biology.

According to Hood, co-founder and president of ISB, before the institute had signed the agreement, it had resolved to create MRM assays for some 20,000 proteins.

"When OriGene came along, they already had purified 5,000 of the proteins, so they were a perfect partner for this collaboration," he says. "By providing ISB with access to one of the largest collections of full length-human protein in the world, this collaboration will rapidly accelerate the validation of ISB's discoveries. Once completed, OriGene will apply the experience and tools developed from such collaboration to develop multiplex protein assays for biomarker discovery and validation. This will be done through collaborations with leading academic and industry researchers in the field of cancer research and autoimmune diseases, for example."

Dr. Wei-Wu He, OriGene's chairman and CEO, points out that this is the first time a 5,000 human protein mass spectrometry standard database will be used to advance and accelerate medical research.

"This unprecedented joint effort of creating a proteotypic PeptideAtlas and SRM/MRM mass spectrometry standard database for 5,000 human proteins will provide extremely important information for the SRM/MRM research community," He says. "Undoubtedly, it will also speed up the pace of its application in novel biomarker discovery."
OriGene brings its 14 years of cDNA cloning and gene centric product development experience into this relationship. According to Hu, OriGene will expand its protein offering to 10,000 in the next year.  

"Currently our 5,000 full-length human proteins is the biggest offering of its kind," Hu points out.  "No other companies or institutes have such a large collection, and this is just the beginning."    

Hood adds that creating assays for all 5,000 of the proteins isn't out of the realm of possibilities.

"I think we will come very close," he says. "Of the 5,000 proteins they have already expressed, they are the easiest 5,000 to express. As we move on and look at some of the other proteins, they will be more difficult to express and thus more difficult to make assays for."

There also are some interesting advantages to the OriGene proteins, Hu notes.
"Another significant advantage with these proteins is they are made in human cell line, HEK293, thus preserving the most authentic protein structure and post-translational modifications (PTMs)," he says. "For example, phospho-protein analysis is a very exciting area in cancer research.  OriGene's proteins are perfect for such applications, whereas E.coli-derived proteins will not be adequate."

Hu points out that field of quantitative proteomics using mass spectrometry is an emerging market, and success will be carefully gauged.

"We will measure our success in two areas: speed of database completion, and quality of peptide sequence data," he says. "Eventually it will be measured by number of people adopting SRM/MRM mass spectrometry using the database, protein standard, and number of publications. The end-game goal would be to develop diagnostic tools to treat human diseases."

OriGene builds world's largest TrueMAB monoclonal antibody facility in China

WUXI, China—OriGene Technologies Inc., with the support of Wuxi Biopharmaceutical R&D Outsourcing Services Park in China, will build one of the largest monoclonal antibody production centers in the world here, the company announced last month.

The new, high-throughput production facility is expected to have more than 1,000 employees with the capacity to produce more than 20,000 TrueMAB antibodies per year.   
OriGene's TrueMAB antibodies are generated using OriGene's large collection of full-length human proteins as primary antigens that have been affinity purified under native conditions to preserve natural protein conformations. As a result, TrueMAB antibodies reportedly provide higher sensitivity and specificity for the recognition of native epitopes on the protein's natural conformational structures.  

OriGene said the new facility will enable it to provide higher quality and greater numbers of monoclonal antibodies to the global research marketplace and address complex applications such as flow cytometry, ELISA, IHC, antibody arrays and Luminex assays.

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