NanoString Technologies

NanoString Technologies, Inc
Public
Traded as NASDAQ: NSTG
Russell 2000 Component
Industry Biotechnology
Founded 2003[1]
Founders Krassen Dimitrov, Amber Ratcliffe, Dwayne Dunaway
Headquarters South Lake Union, Seattle, Washington, United States
Key people
 Brad Gray, CEO
Products nCounter® Analysis System
Revenue $147.6 million[1] (2014)
Total equity $204 million[1] (2015)
Number of employees
 270[1] (2015)
Website www.nanostring.com

NanoString Technologies, Inc. (NASDAQ: NSTG) is a publicly held biotech company that specializes in development of cancer diagnostics tools.[1] The company's technology enables a wide variety of basic research, translational medicine and in vitro diagnostics applications. The company was founded by Krassen Dimitrov, Amber Ratcliffe, and Dwayne Dunaway in 2003,[2][3] and is based in Seattle, Washington.[4] NanoString's "nCounter Analysis System" is based on a digital molecular barcoding technology invented by Dimitrov and Dunaway[5] in Leroy Hood's lab at the Institute for Systems Biology (ISB), and became commercially available in 2008.[6] NanoString received a CE-mark designation for selling the Prosigna breast cancer prognostic gene signature assay (PAM50-based breast cancer test) in Israel and EU in September 2012,[7] and in September 2013, NanoString received FDA 510(k) clearance for Prosigna.[8]

Technology

NanoString's nCounter technology is a variation on the DNA microarray and was invented and patented by Krassen Dimitrov and Dwayne Dunaway.[5][9] It uses molecular "barcodes" and microscopic imaging to detect and count up to several hundred unique transcripts in one hybridization reaction.[10] Each color-coded barcode is attached to a single target-specific probe corresponding to a gene of interest.

The NanoString protocol includes the following steps:

  • Hybridization: NanoString’s Technology employs two ~50 base probes per mRNA that hybridize in solution. The reporter probe carries the signal, while the capture probe allows the complex to be immobilized for data collection.
  • Purification and Immobilization: After hybridization, the excess probes are removed and the probe/target complexes are aligned and immobilized in the nCounter Cartridge.
  • Data Collection: Sample Cartridges are placed in the Digital Analyzer instrument for data collection. Color codes on the surface of the cartridge are counted and tabulated for each target molecule.

Products

NanoString products include:

  • The nCounter Analysis System: The system consists of two instruments: the Prep Station, which is an automated fluidic instrument that immobilizes CodeSet complexes for data collection, and the Digital Analyzer, which derives data by counting fluorescent barcodes. As of March 2015, 264 of these systems were installed around the world, over 50% in research institutions.[1]
  • CodeSets: These are custom-made or pre-designed sets of color-coded probes pre-mixed with a set of system controls.

History

The original patent that is the basis for the nCounter Analysis System was invented and licensed from The Institute for Systems Biology. The business plan was written by Amber Ratcliffe and Aaron Coe and won seed funding in multiple business plan competitions.[11] NanoString was spun out of The Institute for Systems Biology and founded as a separate company in 2003 by Krassen Dimitrov, Amber Ratcliffe and Dwayne Dunaway.

In 2004, NanoString raised its first significant funding in a $4.3M series A financing.[12] They have since raised several more rounds of financing to expand into the development of molecular diagnostics. As of 2011, NanoString Technologies had raised nearly $70M with their series D.[13][14][15]

In 2009, Perry Fell who had been CEO since 2004, left the company abruptly and with no official explanation.[16] Between 2009 and 2010 the company operated with an acting CEO, Wayne Burns.[14][17] Brad Gray, a former Genzyme executive, was hired as president and CEO in 2010.[17]

As of June 2010, the company was not yet profitable.[17] In an interview, Gray suggested that NanoString would begin to develop clinical diagnostics.[17] As of July, 2012, NanoString began indicating a move towards becoming a public company by hiring several senior staff with public company experience.[18] NanoString received a CE-mark designation for selling the Prosigna breast cancer prognostic gene signature assay (PAM50-based breast cancer test) in Israel and EU in September 2012, and in September 2013, NanoString received FDA 510(k) clearance for Prosigna.

In 2013, the company's IPO raised $54 million that was used to expand NanoString sales and marketing efforts. As the result, NanoString revenue has increased by 52% in 2014-2015 financial year.[1]

Scientific reception

A protocol published in Current Protocols in Molecular Biology discussed several advantages and disadvantages of the NanoString technology. The author praised the reproducibility, sensitivity, and low background signal of the technology, and also noted that NanoString does not require amplification of target molecules. The article mentioned the high upfront cost of the necessary instruments as a drawback, and suggested that at least three probes should be used per potential target, which would greatly increase cost and reduce the maximum multiplexing of the technology. According to the author, NanoString represents a middle ground between quantitative PCR and other hybridization microarray technologies.[19] Elsewhere, NanoString technology has been described as highly sensitive.[20]

Publications list

Publication list
  1. Geiss, Gary K; Bumgarner, Roger E; Birditt, Brian; Dahl, Timothy; Dowidar, Naeem; Dunaway, Dwayne L; Fell, H Perry; Ferree, Sean; George, Renee D; Grogan, Tammy; James, Jeffrey J; Maysuria, Malini; Mitton, Jeffrey D; Oliveri, Paola; Osborn, Jennifer L; Peng, Tao; Ratcliffe, Amber L; Webster, Philippa J; Davidson, Eric H; Hood, Leroy; Dimitrov, Krassen (2008). "Direct multiplexed measurement of gene expression with color-coded probe pairs". Nature Biotechnology. 26 (3): 317–25. doi:10.1038/nbt1385. PMID 18278033.
  2. Materna, Stefan C.; Nam, Jongmin; Davidson, Eric H. (2010). "High accuracy, high-resolution prevalence measurement for the majority of locally expressed regulatory genes in early sea urchin development". Gene Expression Patterns. 10 (4–5): 177–84. doi:10.1016/j.gep.2010.04.002. PMC 2902461. PMID 20398801.
  3. Dixit, Evelyn; Boulant, Steeve; Zhang, Yijing; Lee, Amy S.Y.; Odendall, Charlotte; Shum, Bennett; Hacohen, Nir; Chen, Zhijian J.; Whelan, Sean P.; Fransen, Marc; Nibert, Max L.; Superti-Furga, Giulio; Kagan, Jonathan C. (2010). "Peroxisomes Are Signaling Platforms for Antiviral Innate Immunity". Cell. 141 (4): 668–81. doi:10.1016/j.cell.2010.04.018. PMC 3670185. PMID 20451243.
  4. Nam, J.; Dong, P.; Tarpine, R.; Istrail, S.; Davidson, E. H. (2010). "Functional cis-regulatory genomics for systems biology". Proceedings of the National Academy of Sciences. 107 (8): 3930–5. Bibcode:2010PNAS..107.3930N. doi:10.1073/pnas.1000147107. JSTOR 40537388. PMC 2840491. PMID 20142491.
  5. Smith, Elizabeth R.; Cai, Kathy Qi; Smedberg, Jennifer L.; Ribeiro, Melina M.; Rula, Malgorzata E.; Slater, Carolyn; Godwin, Andrew K.; Xu, Xiang-Xi (2010). Bauer, Joseph Alan, ed. "Nuclear Entry of Activated MAPK is Restricted in Primary Ovarian and Mammary Epithelial Cells". PLoS ONE. 5 (2): e9295. Bibcode:2010PLoSO...5.9295S. doi:10.1371/journal.pone.0009295. PMC 2823791. PMID 20174585.
  6. Ouellet, Mario; Adams, Paul D; Keasling, Jay D; Mukhopadhyay, Aindrila (2009). "A rapid and inexpensive labeling method for microarray gene expression analysis". BMC Biotechnology. 9: 97. doi:10.1186/1472-6750-9-97. PMC 2790446. PMID 19939278.
  7. Amit, Ido; Garber, Manuel; Chevrier, Nicolas; Leite, Ana Paula; Donner, Yoni; Eisenhaure, Thomas; Guttman, Mitchell; Grenier, Jennifer K.; Li, Or; Zuk, Lisa A.; Schubert, Brian; Birditt, Tal; Shay, Alon; Goren, Xiaolan; Zhang, Zachary; Smith, Raquel; Deering, Rebecca C.; McDonald, Moran; Cabili, Bradley E; Bernstein, John L.; Rinn, Alex; Meissner, David E.; Root, Nir; Hacohen, Aviv; Regev, A. (2009). "Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses". Science. 326 (5950): 257–63. Bibcode:2009Sci...326..257A. doi:10.1126/science.1179050. PMC 2879337. PMID 19729616.
  8. Palamanda, Jairam; Kumari, Pramila; Murgolo, Nicholas; Benbow, Larry; Lin, Xinjie; Nomeir, Amin (2009). "Evaluation of CYP1A1 and CYP2B1/2 m-RNA Induction in Rat Liver Slices Using the NanoString® Technology: A Novel Tool for Drug Discovery Lead Optimization". Drug Metabolism Letters. 3 (3): 171–5. doi:10.2174/187231209789352094. PMID 19702544.
  9. Payton, Jacqueline E.; Grieselhuber, Nicole R.; Chang, Li-Wei; Murakami, Mark; Geiss, Gary K.; Link, Daniel C.; Nagarajan, Rakesh; Watson, Mark A.; Ley, Timothy J. (2009). "High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples". Journal of Clinical Investigation. 119 (6): 1714–26. doi:10.1172/JCI38248. PMC 2689138. PMID 19451695.
  10. Malkov, Vladislav A; Serikawa, Kyle A; Balantac, Noel; Watters, James; Geiss, Gary; Mashadi-Hossein, Afshin; Fare, Thomas (2009). "Multiplexed measurements of gene signatures in different analytes using the Nanostring nCounter™ Assay System". BMC Research Notes. 2: 80. doi:10.1186/1756-0500-2-80. PMC 2688518. PMID 19426535.
  11. Su, Yi-Hsien; Li, Enhu; Geiss, Gary K.; Longabaugh, William J.R.; Krämer, Alexander; Davidson, Eric H. (2009). "A perturbation model of the gene regulatory network for oral and aboral ectoderm specification in the sea urchin embryo". Developmental Biology. 329 (2): 410–21. doi:10.1016/j.ydbio.2009.02.029. PMC 2677136. PMID 19268450.
  12. Birtwell, Sam; Morgan, Hywel (2009). "Microparticle encoding technologies for high-throughput multiplexed suspension assays". Integrative Biology. 1 (5–6): 345–62. doi:10.1039/B905502A. PMID 20023742.

References

  1. 1 2 3 4 5 6 7 Annie Zak (20 March 2015). "NanoString pulls in 52% more sales". Puget Sound Business Journal. 35 (48). Seattle: American City Business Journals. p. 39. ISSN 8750-7757. LCCN 99107105. OCLC 11683053.
  2. ↑ Kimberly Stegmaier. "Krassen Dimitrov of ISB on Business and Better Microarray Labels | BioArray News | Arrays". GenomeWeb. Retrieved 2012-10-14.
  3. ↑ Nocera, Joseph (2004-04-05). "A Tale Of Two Companies One started in 1955 and is in the FORTUNE 500. The other started five months ago and doesn't have an office yet. What it takes to reach the pinnacle of business. - April 5, 2004". Money.cnn.com. Retrieved 2012-10-14.
  4. ↑ http://seattletimes.nwsource.com\html\businesstechnology\2002002077_nanostring11.html
  5. 1 2 "Methods for detection and quantification of analytes in complex mixtures - The Institute for Systems Biology". Freepatentsonline.com. 2008-08-20. Retrieved 2012-10-16.
  6. ↑ "Lee Hood's Proteges Strike Again: Nanostring Ships Its First Commercial Cell Analyzer". Xconomy. Retrieved 2012-10-14.
  7. ↑ "NanoString Gets EU Clearance To Sell Breast Cancer Diagnostic Test". Xconomy. 2012-09-27. Retrieved 2012-10-14.
  8. ↑ "NanoString Wins FDA Approval of Breast Cancer Diagnostic Test". Xconomy. 2013-09-09. Retrieved 2013-09-09.
  9. ↑ "United States Patent: 7919237". Patft.uspto.gov. Retrieved 2012-10-14.
  10. ↑ Geiss, Gary K; Bumgarner, Roger E; Birditt, Brian; Dahl, Timothy; Dowidar, Naeem; Dunaway, Dwayne L; Fell, H Perry; Ferree, Sean; George, Renee D; Grogan, Tammy; James, Jeffrey J; Maysuria, Malini; Mitton, Jeffrey D; Oliveri, Paola; Osborn, Jennifer L; Peng, Tao; Ratcliffe, Amber L; Webster, Philippa J; Davidson, Eric H; Hood, Leroy; Dimitrov, Krassen (2008). "Direct multiplexed measurement of gene expression with color-coded probe pairs". Nature Biotechnology. 26 (3): 317–25. doi:10.1038/nbt1385. PMID 18278033.
  11. ↑ Puget Sound Business Journal (2003-05-27). "UW startup wins second business plan competition - Puget Sound Business Journal". Bizjournals.com. Retrieved 2012-10-14.
  12. ↑ "NanoString Technologies" (PDF). Nanostring.com. Retrieved 2012-10-16. {pdf}
  13. ↑ NanoString Technologies (2011-11-07). "Press Release | NanoString Technologies". Nanostring.com. Retrieved 2012-10-14.
  14. 1 2 "NanoString Technologies Closes $30 million Series C Financing to Accelerate the Commercialization of its Leading Expression Prof". FierceBiotech. Retrieved 2012-10-14.
  15. ↑ "NanoString Adds $2.5M Financing". Xconomy. 2011-06-30. Retrieved 2012-10-14.
  16. ↑ "NanoString CEO Perry Fell Departs". Xconomy. 2009-03-24. Retrieved 2012-10-14.
  17. 1 2 3 4 "NanoString Hires Genzyme Vet as CEO to Lead Foray Into Molecular Diagnostics". Xconomy. 2010-06-29. Retrieved 2012-10-14.
  18. ↑ "NanoString Makes IPO Prep Move, Adds Finance Vet to Board". Xconomy. 2012-07-18. Retrieved 2012-10-14.
  19. ↑ Kulkarni, Meghana M. (2011). "Digital Multiplexed Gene Expression Analysis Using the NanoString nCounter System". Current Protocols in Molecular Biology. 25B.10.1–25B.10.17. doi:10.1002/0471142727.mb25b10s94. ISBN 978-0-471-14272-0. PMID 21472696.
  20. ↑ Zak, Daniel E; Aderem, Alan (2009). "A systems view of host defense". Nature Biotechnology. 27 (11): 999–1001. doi:10.1038/nbt1109-999. PMC 3076594. PMID 19898453.
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