NanoString Technologies

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NanoString Technologies is a privately held life sciences company that specializes in gene expression profiling.^[1] The company was founded by Krassen Dimitrov^[2] in 2003^[3] and is based in Seattle, Washington.^[4] NanoString's "nCounter Analysis System" is based on a digital molecular barcoding technology invented by Dimitrov in Leroy Hood's lab at the Institute for Systems Biology (ISB), and became commercially available in 2008.^[5]

Technology

The Nanostring technology is a variation on the DNA microarray and was invented and patented by Krassen Dimitrov.^[6] It uses molecular "barcodes" and microscopic imaging to detect and count up to several hundred unique transcripts in one hybridization reaction.^[7] 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.
• CodeSets: These are custom-made or pre-designed sets of color-coded probes pre-mixed with a set of system controls.

History

NanoString was founded in 2003 and is not profitable^[8] Between 2009 and 2010 the company operated for over a year without a chief executive officer.^[8] Brad Gray, a former Genzyme executive, was hired as president and CEO in 2010.^[8] In an interview, Gray suggested that NanoString would need to focus on the more rewarding but high-stakes field of clinical diagnostics.^[8]

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.^[9] Elsewhere, NanoString technology has been described as highly sensitive.^[10]

Publications list

1. Geiss, G.K. et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature Biotechnology 26: 317-25 (2008).
2. Materna, S.C. et al. High accuracy, high-resolution prevalence measurement for the majority of locally expressed regulatory genes in early sea urchin development. Gene Expression Patterns doi:10.1016/j.gep.2010.04.002 (2010).
3. Dixit et al. Peroxisomes Are Signaling Platforms for Antiviral Innate Immunity. Cell 6 May 2010; doi:10.1016/j.cell.2010.04.018
4. Nam, J., Dong, P., Tarpine, R., Istrail, S., Davidson, E.H. Functional cis-regulatory genomics for systems biology. Proc Natl Acad Sci USA 23 February 2010;107(8):3930-5. Epub 8 February 2010.
5. Smith, E.R., Cai, K.Q., Smedberg, J.L., Ribeiro, M.M., Rula, M.E., Slater, C., Godwin, A.K., Xu, X.X. Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells. PLoS One 18 February 2010;5(2):e9295.
6. Ouellet, M. et al. A rapid and inexpensive labeling method for microarray gene expression analysis. BMC Biotechnology 25 November 2009;9(1):97. Epub ahead of print.
7. Amit, I. et al. Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses. Science 9 October 2009; Vol. 326. no. 5950, pp. 257–263.
8. Palamanda, J.R. et al. 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 2009 Aug;3(3):171-5. Epub 1 August 2009.
9. Payton, J.E. et al. High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples. The Journal of Clinical Investigation 119(6): 1714–1726 (2009).
10. Vladislav, M.A. et al. Multiplexed measurements of gene signatures in different analytes using the NanoString nCounter Assay System. BMC Research Notes 2: 80 (2009).
11. Yi-Hsien Su et al. A Perturbation Model of the Gene Regulatory Network for Oral and Aboral Ectoderm Specification in the Sea Urchin Embryo. Developmental Biology 329: 410-421 (2009).
12. Birtwell, S. et al. Microparticle encoding technologies for high-throughput multiplexed suspension assays. Integrative Biology 1: 227-436 (2009).

References

External links

• Additional information on miRNA
• Additional information on gene expression
• Additional information on copy number variation
• VIB Microarray Facility: NanoString Service Provider (Europe)