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Promega

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Promega Corporation
File:Logo Promega.png
Type Private
Founded 1978 Madison, Wisconsin as Biotec
Location Madison, Wisconsin headquarters
Key people William A. Linton Chairman and CEO
Industry Biotechnology
Revenue $220 million USD (2007)
Employees ~950 worldwide (2008)
Website http://www.promega.com/


History and Background

In 1978 scientists were just beginning to understand the potential of what Boyer and Cohen had done by cutting DNA into specific fragments using restriction enzymes, rejoining them and transferring them into bacterial host cells [1]. Promega Corporation founder and CEO, Bill Linton, realized that if researchers had these enzymatic tools readily available to them, they would have more freedom to focus on their research question: “What does that piece of DNA do in the cell?”

The industry of biotechnology got its start with Boyer and Cohen’s patents on recombinant DNA technology. Promega Corporation got its start in Bill Linton’s laboratory in 1978 with the isolation of a few restriction enzymes[2].

Promega now offers more than 2,000 life science products to research scientists in the fields of genetic identity/forensics, proteomics, molecular diagnostics, cellular analysis, drug discovery, and of course, genomics[3].

Promega Corporation Headquarters in the Agora, Fitchburg Center, Madison, WI, USA.

The privately held company has been profitable since 1984 and has its headquarters in Madison, WI, USA. Its global reach includes branch offices in 13 countries and manufacturing facilities in San Luis Obispo, California, USA; Shanghai, China; and Seoul, South Korea[3]. From 2006 to 2007, company revenues grew by more than 10% to 220 million dollars (US) with approximately 12% reinvested in research and development[4]. Promega Corporation also established the first biotechnology joint venture in China (Sino-American Biotechnology Co. in 1985)[5].

As of 2008, 145 US patents were assigned to Promega Corporation, and the company holds a number of foreign patents as well[6]. In addition to developing its own intellectual property, Promega works with academic institutions and other entities to license and develop promising technologies[4]. As a member of the Wisconsin Alumni Research Foundation Research Tool Subscription Program, Promega has the opportunity to take a first look at new technologies from the university[7].

Promega has developed new methods of delivery to laboratory scientists, such as an on-site stocking system, which uses radio frequency identification (RFID) linked to the internet to track and manage remote inventory. This technology ultimately resulted in the spin-off company Terso Solutions that specializes in the design and manufacture of small RFID storage units [8].

Product Areas and Technologies

Genomics

Promega's portfolio began with products for genomics researchers and now includes coordinated cloning systems, new generation luciferase reporters, and amplification products as well as the original restriction and modifying enzymes. The Promega portfolio of amplification products includes the GoTaq® family of polymerases and buffers and the Plexor® quantitative PCR system.

Genetic Identity and Forensics

Promega is one of two main companies worldwide that provide systems to scientists for genetic identification based on DNA analysis using short tandem repeats (STRs)[3],[9].

DNA-based human identification or DNA finger-printing was originally developed by Sir Alec Jefferys, who identified repetitive regions of human genomic DNA. These regions vary in length based on the number of repeats (variable number of tandem repeats, VNTR)[10][11]. Individuals possess different numbers of repeats in these sequences, which can be detected on gels and used as an unique identifier for an individual. VNTRs were used in an immigration case in 1985[10][11]; since that time improvements in DNA isolation and detection have made DNA-based identification a standard in forensic and medical laboratories.

Current DNA-based identification methods are based on PCR amplification of STR loci. Promega was the first company to provide kits for STR analysis of single loci[9]. Along with Applied Biosystems, Promega participated with the FBI and other crime labs in validating STR loci that would eventually be selected as the core loci for the COmbined DNA Index System (CODIS), used for forensic DNA testing in North America.

The Promega PowerPlex® STR systems were the first commercially available systems for STR analysis that contained all of the CODIS loci[9]. These systems have been used to identify the remains of victims found in mass graves from wars in Croatia, Bosnia and Herzegovina in the early 1990s[12]. Promega also sent scientists to New York immediately after the September 11, 2001, attack on the World Trade Center to assist in identifying victims [3].

Proteomics

The development of eukaryotic cell-free translation systems based on rabbit reticulocyte lysate (RRL) was a major advance for studying protein function[13]. Promega Corporation was an early supplier in the cell-free protein synthesis field and is continuing to develop its portfolio in this area[14]. Since the introduction of the original RRL systems, coupled transcription and translation systems, which use DNA rather than the more labile RNA as the template, have become available[13]. Additionally, researchers now have the option of using nonradioactive methods to detect and capture proteins, and they can synthesize proteins on a large or small scale, depending on their experimental needs[15].

The sequencing of the human genome in 2003 ushered in an era of high-throughput proteomics. With the gene sequences readily available, researchers’ questions turned to the function of protein-coding sequences within the genome and the interactions between protein networks driving cellular processes[14]. For example, Promega TnT® systems have been used in a high-throughput protein truncation test-ELISA screen for mutations of the ataxia-telangiectasia mutated (ATM) gene that disrupt full-length protein synthesis[16]. Studying networks of proteins requires expression of large numbers of proteins from expansive cDNA libraries. The Promega Flexi® Vector Cloning System was used in constructing both the KDRI HUGE collection of full-length cDNA clones and the commercially available Origene FlexClone collection[17].

The Promega HaloTag® Technology Platform is a is based on a modified halogenase that forms a covalent bond with synthetic ligands.[18]. A researcher “tags” a protein of interest by creating a fusion with the HaloTag® protein. Then one of several ligands can be used to visualize, capture, and track proteins[18]. HaloTag® technology is being incorporated into commercially available open reading frame libraries to create ready-to-use expression clones[19].

Cellular Analysis and Drug Discovery

Promega offers a range of products that are built upon bioluminescence technology.

Cell-based assays that use bioluminescence eliminate many problems associated with overlap between test compound excitation/emission wavelengths and fluorescent reporters, which can confound assay results[20]. Luciferase is not endogenous to mammalian cells, and therefore inherent background is reduced, dramatically increasing assay sensitivity that allows researchers to conserve precious cell samples and detect signals from a subset of a mixed cell population[20].

One of the most recognized bioluminescence-based assays is the Dual-Luciferase® Reporter Assay, which allows researchers to differentiate changes in signal that are biologically relevant from nonspecific changes through normalization to a control[20]. Such dual-luciferase reporter assays are used to monitor activity of G-protein coupled receptor pathways[20], investigate modulation of gene activity through antioxidant response elements[21], and identify molecules that enhance STAT-1-dependent gene expression in a high-throughput screen[22].

By modifying the bioluminescence approach so that ATP or luciferin rather than luciferase is the limiting reagent, Promega has developed assays that allow researchers to measure parameters other than gene activity. For instance, assays for kinase inhibitors are of particular interest to the drug discovery community, and luminescent assays such as the Kinase-Glo® Assays provide a universal screening method for identifying inhibitors using virtually any kinase and substrate combination[20].

Additionally, since ATP is a marker of cell viability, ATP assays are used to detect microbes and quantify mammalian cells[20]. Bioluminescent ATP-based cell viability assays, such as the CellTiter-Glo® Assay, are more sensitive than methods that assess redox potential in cells, and additionally the CellTiter-Glo® Assay requires only minutes (compared to hours) to perform[20]. The widespread use of bioluminescence-based technologies for screening is demonstrated by a search of the PubChem BioAssay database, which has 131 entries that describe Promega technologies or assays used by MLSCN screening centers[23].

Biological probes and drug candidates identified during screening must be characterized further for adsorption, deposition, metabolism excretion and toxicology (ADME/Tox). Traditionally, ADME/Tox assays are performed in animal models, but animal testing is expensive, raises moral questions, and may not be truly predictive, so drug developers are turning to cell-based and in vitro assays[24]. Bioluminescence-based screening technologies may help drug developers eliminate toxic compounds earlier in the development process, reducing failed clinical trials or after-market recalls[20][25][26][27].

Cytochrome P450 (CYP450) enzymes are involved in metabolism and clearance of many drugs and therefore are involved in toxicity and drug-drug interactions (DDI). In the P450-Glo™ Assays a luminogenic substrate is metabolized by a CYP450 to a luciferin derivative, which then reacts with luciferase to produce light.

By combining luciferase reporter gene assays and luminogenic P450 assays, researchers can predict induction of cytochrome P450 activity at the level of gene transcription and enzyme activity. This approach was useful for understanding the harmful interation between grapefruit juice and statins. A component of grapefruit juice, bergamottin, upregulates the gene encoding the cytochrome P450 that metabolizes the cholesterol-lowering statins, but at the same time, bergamottin inhibits the activity of the actual enzyme, slowing statin clearance[25].

Integrated Platforms

Promega bioluminescence assays, DNA and RNA purification chemistries, and HaloTag® technologies integrate with the high-throughput automated systems found in many laboratories. Some of this integration has occurred through collaboration with instrument manufacturers.

Promega also sells the Maxwell® 16 System, which is a bench-top automated purification system for lower throughput research and diagnostic laboratories. The Maxwell® 16 System purifies DNA, RNA, and recombinant protein and processes up to 16 samples in 30–45 minutes, depending on sample type. This system has been used to purify proteins for structural studies[28] and to purify DNA from a variety of sample types and organisms[29].

Promega GloMax® Luminometers are supplied with preinstalled protocols that allow researchers to perform multiplex bioluminescent assays. The luminometers with injection systems are available for use with dual-reporter assays like the Dual-Luciferase® systems.

Molecular Diagnostics

The Promega Maxwell® 16 System is compliant as a General Purpose Medical Device in the United States and has received the CE Mark for diagnostic use throughout the European Union[30]. This bench-top, personalized approach to automation allows clinical labs to benefit from more reproducible results and improved work flow with easy installation and minimal training[31][32].

The Y-Chromosome Deletion Detection System from Promega also carries the CE Mark for use as an in vitro diagnostic device in the European Union.

Manufacturing

Promega was first certified to international standards for quality management systems in 1998 and is currently certified to the ISO 13485 standard, required for the development, manufacture, testing, and delivery of medical devices around the world. The ISO series of quality management system standards are developed and maintained by the International Organization for Standardization. An organization achieving ISO certification has demonstrated to a third-party body of experts that the organization meets all requirements of the standard.

Corporate Citizenship and Environmental Record

According to Jim Leonhart, Executive Director of the Wisconsin Biotechnology and Medical Device Association,

Prairie surrounding the Agora at Fitchburg Center helps with sustainable development by providing natural habitat for many species.

Promega Corporation is not only a leader in the biotechnology industry, but it is also a “good corporate citizen” (3). When Promega broke ground for the BioPharmaceutical Technology Center (BTC) in 1994, 20,000 square feet of that building was devoted to community use, including a 300-seat auditorium, conference rooms, and teaching labs that are part of the BioPharmaceutical Technology Center Institute (BTCI), a nonprofit organization of which Promega is the founder and main corporate sponsor[3][4][33][34]. Activities hosted by BTCI include the Annual International Bioethics Forum, the Stem-Cell Symposium, and the laboratory course for the Youth Apprenticeship Program in Biotechnology[34].

In addition to the outreach provided through the BTCI, Promega runs a Training Support Program that provides Promega products at significant discounts to educators in the US and provides free educational resources for undergraduate instructors. The BTC Atrium Gallery also hosts quarterly art shows that feature local artists.

In 1994, Promega built the BTC, native prairie landscaping was used to reduce application of herbicides and fertilizers and sustain wildlife habitat[35].

The prairie and rain gardens provide a natural filtering system for runoff.

The Agora, which opened in November 2006, is the focal point of Fitchburg Center and the headquarters for Promega Corporation. This building retains Promega’s commitment to environmentally friendly design. The building has a storm water collection system that allows runoff to drain into the adjacent prairie for natural filtering and underground parking to minimize the amount of asphalt and concrete associated with development of the area[36].

Additionally, Promega practices environmentally responsible shipping and packaging, reducing disposable packaging materials whenever possible and using recycled materials for packaging and print materials. For large shipments to Europe, Promega uses Enviro Containers.

Footnotes

  1. ^ "Inventor of the Week: Archive". Retrieved November 11, 2008.
  2. ^ "Promega eNotes - Feature". Retrieved November 11, 2008.
  3. ^ a b c d e "madison.com". Retrieved November 11, 2008.
  4. ^ a b c "Promega Corporation: Wisconsin's quiet innovator (WTN News)". Retrieved November 11, 2008.
  5. ^ "madison.com". Retrieved November 11, 2008.
  6. ^ United States Patent and Trademark Office Web site search for Patents Assigned to Promega Corporation. Retrieved on July 1, 2008.
  7. ^ "Promega to get early access to WARF technologies under new agreement (WTN News)". Retrieved November 11, 2008..
  8. ^ 2005 Report: Promega spins off RFID unit. The Capital Times. November 15. Business, 8B. Retrieved on July 7, 2008.
  9. ^ a b c Amplification on-line training course at DNA.gov(Note: The amplification course requires registration)
  10. ^ a b Donelly, S. (2007) An interview with Sir Alec Jefferys. Profiles in DNA September. 3–5. Retrieved July 14, 2008.
  11. ^ a b History of DNA Analysis. Retrieved July 14, 2008
  12. ^ Alonso A, Andelinović S, Martín P; et al. (2001). "DNA typing from skeletal remains: evaluation of multiplex and megaplex STR systems on DNA isolated from bone and teeth samples" (PDF). Croat. Med. J. 42 (3): 260–6. PMID 11387635. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ a b Arduengo, M., Schenborn, E. and Hurst, R. (2007) The Role of Cell -Free Rabbit Reticulocyte Expression Systems in Functional Proteomics. In: Cell-Free Protein Expression. Kudlicki, W. et al. (ed.) Landis Bioscience (Austin, TX). ISBN 978-1-58706-123-3
  14. ^ a b Zhao KQ, Hurst R, Slater MR, Bulleit RF (2007). "Functional protein expression from a DNA based wheat germ cell-free system". J. Struct. Funct. Genomics. 8 (4): 199–208. doi:10.1007/s10969-007-9035-2. PMID 18034374. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ Kobs, G. (2008) Selecting the cell-free protein expression system that meets your experimental goals. Cell Notes 21, 6–9. (accessed July 17, 2008)
  16. ^ Du, L. et al. (2008) Rapid screen for truncating ATM mutations by PTT-ELISA. Mutat. Res. 640, 139–44.
  17. ^ Temple, G. (2006) From genome to proteome: Developing expression clone resources for the human genome. Hum. Mol. Genet. 15, R31–R43
  18. ^ a b Los, G. et al. (2008) HaloTag: A novel protein labeling technology for cell imaging and protein analysis. ACS Chem. Biol. 3, 373–82.
  19. ^ Anderson, C. (2008) Promega and GeneCopoeia play tag. Drug Discovery News. June.(accessed July 17, 2008)
  20. ^ a b c d e f g h Fan, F. and Wood, K.V. (2007) Bioluminescent assays for high-throughput screening. ASSAY and Drug Development Technologies. 5, 127–36.
  21. ^ Wruck, C.J. et al. (2008) Kavalactones protect neural cells against amyloid-β peptide-induced neurotoxicity via ERK 1/2-dependent Nrf-2 activation. Mol. Pharmacol.. 73, 1785–95.
  22. ^ Lynch, R.A. et al. (2007) A small-molecule enhancer of signal transducer and activator of transcription 1 transcriptional activity accentuates the antiproliferative effects of IFN-γ in human cancer cells. Cancer Research 67, 1254-61.
  23. ^ The [http://www.ncbi.nlm.nih.gov/sites/entrez?holding=wipmglib PubChem BioAssay Database] was searched for the keyword “promega” and returned 131 results. (July 18, 2008)
  24. ^ Dove, A. (2007) ADME-Tox gets faster, cheaper and safer. Drug Discovery and Development. September 24. (accessed July 18, 2008)
  25. ^ a b Lipp, E. (2008) Tackling drug-interaction issues early on. Genetics Engineering News 28, 12.(accessed July 18, 2008)
  26. ^ Cali, J.J. (2008) Bioluminescent assays for ADMET. Expert Opin. Drug Metab. Toxicol. 4, 103–20.
  27. ^ Cali, J.J. (2006) Luminogenic cytochrome P450 assays. Expert Opin. Drug Metab. Toxicol. 2, 629–45.
  28. ^ Frederick, R. (2007) Three-part, small-scale screening platform for the masses. Center for Eukaryotic Structural Genomics. Department of Biochemistry. University of Wisconsin Madison. PowerPoint® Presentation (accessed July 18, 2008)
  29. ^ Maxwell® Applications Database(accessed July 18, 2008)
  30. ^ (2008) Promega gets CE Mark for DNA purification system. GenomeWeb Daily May 29. (accessed July 18, 2008)
  31. ^ Berman, R. et al. (2007) Automated sample prep to improve lab workflow. Automation for diagnostics: IVD Technology Supplement Sept. 11.
  32. ^ Thomson, A. (2007) Insights into lab automation’s future. IVD Technology January, 66.
  33. ^ Howell, B. (2003) The science of cool. Madison Magazine. (accessed July 2, 2008)
  34. ^ a b BioPharmaceutical Technology Center Institute (accessed July 7, 2008)
  35. ^ Prairie Nursery Case Study.(accessed July 7, 2008)
  36. ^ Ivey, M. (2006) Written in Stone: Fitchburg town center embraces environment. The Capital Times. Sept. 14. (accessed July 7, 2008)


External Links

Promega Corporation

BioPharmaceutical Technology Center Institute

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