NanoString Technologies, Inc. (NASDAQ: NSTG) is a publicly held provider of life science tools for translational research and molecular diagnostics. 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, and is based in Seattle, Washington. NanoString's "nCounter Analysis System" is based on a digital molecular barcoding technology invented by Dimitrov and Dunaway in Leroy Hood's lab at the Institute for Systems Biology (ISB), and became commercially available in 2008. 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.
NanoString's nCounter technology is a variation on the DNA microarray and was invented and patented by Krassen Dimitrov and Dwayne Dunaway. It uses molecular "barcodes" and microscopic imaging to detect and count up to several hundred unique transcripts in one hybridization reaction. 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.
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.
CodeSets: These are custom-made or pre-designed sets of color-coded probes pre-mixed with a set of system controls.
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. 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. 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.
In 2009, Perry Fell who had been CEO since 2004, left the company abruptly and with no official explanation. Between 2009 and 2010 the company operated with an acting CEO, Wayne Burns. Brad Gray, a former Genzyme executive, was hired as president and CEO in 2010.
As of June 2010, the company was not yet profitable. In an interview, Gray suggested that NanoString would begin to develop clinical diagnostics. As of July, 2012, NanoString began indicating a move towards becoming a public company by hiring several senior staff with public company experience. 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.
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. Elsewhere, NanoString technology has been described as highly sensitive.
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 Biotechnology26 (3): 317–25. doi:10.1038/nbt1385. PMID18278033.
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 Letters3 (3): 171–5. doi:10.2174/187231209789352094. PMID19702544.