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CustomArray Nets $200K from NIH to Develop Padlock-Probe Detection System for Cancer Dx


This story was originally posted on Dec. 9

By Justin Petrone

The National Institutes of Health recently awarded CustomArray nearly $200,000 to develop its padlock-probe array technology for use in microRNA detection, with an eye on eventually making the platform available to support oncology testing.

Brooke Anderson, CustomArray's chief operations officer, told BioArray News last week that the work is "at an early stage," and that it relies on CustomArray's ability to synthesize pools of oligonucleotides using its B3 synthesizer.

Privately held CustomArray, based in Mukilteo, Wash., was founded last year to continue CombiMatrix's microarray business after that firm restructured to focus on its molecular diagnostics business (BAN 1/25/2011). While CustomArray has positioned itself as a tools and services provider for research applications, like sequence capture and miRNA expression profiling, it seems that a move into diagnostics may be in its future too, according to its new grant.

Entitled, "Adapting padlock-probe detection systems to ncRNA detection for cancer diagnostics," the $198,722 grant was awarded through the National
Cancer Institute this year, but with no public grant date or project duration. The project leader is John Cooper, principal scientist at CustomArray.

According to the grant's abstract, CustomArray is seeking to develop a cancer diagnostic based on miRNA expression patterns found in human serum. The firm claims that it can already diagnose whether an individual with cancer has one of five different diseases.

CustomArray said in the abstract that in a data set involving 246 patient-derived serum samples, it was able to distinguish cancer-derived sera from normal controls with a sensitivity of 76 percent and a specificity of 84 percent.

"These data, though promising, also indicated to us that a more sensitive assay is necessary in order to resolve these distinct patterns of miRNA expression," the firm said in the abstract.

To accomplish this, it aims to develop a multiplexed padlock-probe assay on its microarray platform that will detect most of the known human miRNAs. Anderson said that the company will rely on its B3 custom oligo synthesizer, which was originally sold for array fabrication but always was capable of synthesizing oligo pools.

According to Anderson, the B3 CustomArray can synthesize oligo pools of 12,000 to 90,000 different oligos of arbitrary sequence up to about 200 bases in length. The pools, which are synthesized in situ on arrays before being cleaved for solution-phase use, are "available at a much lower cost than traditional column synthesis," Anderson claimed.

"This significantly changes the price points of some newer applications such as gene assembly and solution-based targeted sequencing for custom regions," he said. "We envisioned that these pools could also be used in other solution-based assays, such as for microRNA profiling, with advantages including low cost of iterations during development and not skewing expression profiles yet still giving good sensitivity."

According to the abstract, the B3 should permit CustomArray to produce both the padlock probes and to detect signal from the amplified mixture. The firm said that it hopes to use its proposed assay to investigate the extracellular structures that protect the miRNA molecules that are secreted by proliferating tumor cells. Once it develops assays, CustomArray aims to look for patterns of miRNA and other ncRNA expression from normal and cancer patient serum samples.

Anderson declined to provide additional detail. "Our longer-term plans depend on how things go," he said, "but I suspect that we probably will try to apply for more funding and to expand the work."

CustomArray is not alone in its effort to adapt its in situ oligo synthesis capabilities for use in diagnostics. Heidelberg, Germany-based Febit, for instance, restructured last year to focus on miRNA biomarker discovery using its Geniom biochip synthesis platform (BAN 6/29/2010).

Have topics you'd like to see covered in BioArray News? Contact the editor a1t jpetrone [at] genomeweb [.] com.

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