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Silicon Valley Startup Cell Data Sciences Aims to Improve Nucleic Acid Yield from FFPE

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NEW YORK (GenomeWeb) – Startup firm Cell Data Sciences has won a grant from the National Institutes of Health to develop a method to enhance retrieval of nucleic acids from formalin-fixed, paraffin-embedded tissues.

The new funding, worth $180,000 over the next six months, was awarded last week by the NIH's National Cancer Institute as part of a call for translational and clinical investigations that encompass cancer prevention, diagnosis, and treatment.

Founded last year by researchers from Stanford University, Silicon Valley-based Cell Data Sciences will commercialize a chemical catalyst that liberates DNA and RNA from the crosslinks and adducts formed during FFPE processing. The company plans to bring this technology to market in the coming months.

The method chemically enables removal of RNA and DNA from FFPE under milder temperature and pH conditions than are required currently. It also appears to be the first technology of its kind, Lucian Orbai, a co-founder of Cell Data Sciences, told GenomeWeb in an interview this week.

"Generally the way folks have tried to solve the problem of getting molecular information out of FFPE samples was through work-arounds," Orbai said.

The most typical way is to use high heat, but this tends to degrade nucleic acids, especially RNA. The resulting short fragments can lead to additional problems in downstream PCR or sequencing. Other groups have developed work-arounds like using higher concentrations of reagents in downstream processing, as previously reported.

"What we tried to do was to actually look at the specific chemical adducts and crosslinks that are formed by the formaldehyde and to use a chemical catalyst that removes them," Orbai explained.

Orbai noted that the founders of the company — including Eric Kool, a Stanford researcher known for work on unnatural base pairs — are all nucleic acid chemists, so they approach RNA and DNA at a fairly fundamental level and have experience "making and changing the chemical structure of DNA and RNA."

The catalyst itself is water-soluble and "bifunctional," containing both an amine and a proton-donating group.

An initial study of the catalyst-based technique was published online earlier this month in Nature Chemistry.

That work found a seven- to 25-fold increase in RNA yield as analyzed by RT-qPCR compared to a "market leading" kit, the AllPrep DNA/RNA FFPE kit from Qiagen.

The study also showed it enhanced yield over a literature-standard method requiring high heat and Tris buffer which led to greater than 40 percent degradation of RNA after 12 hours. Meanwhile, a "milder" incubation with the firm's catalyst at 37 °C for 12 to 18 hours was effective at recovering a high yield of RNA.

However, Orbai noted that these specific conditions are variables that are being optimized and will likely be different for particular applications. The variables in the Nature Chemistry paper were also used to better compare the method to the Qiagen FFPE kit, so the techniques in the forthcoming commercial product may be different.

Pre-PCR processing steps used for FFPE blocks have previously been shown to be a source of variability between clinical labs examining cancer-related genes, with one study finding issues with measurements of DNA quantity, purity, and integrity from standardized samples, as previously reported

The catalyst technique might help solve this problem by providing higher yields of nucleic acids. It also provides larger fragments, which would be useful for PCR-base applications, as well as next-generation sequencing or microarray analyses.

The typical FFPE sample is often a small bit of tissue, like a needle biopsy core. "It can be difficult to extract enough material, so using FFPE samples efficiently is important, and we think we can help with that," Orbai said.

The technology overall consists of more than just the chemical structure of the catalyst, and Orbai, who previously worked as a biotech patent attorney after earning a PhD in Kool's lab, noted that the firm has filed patents around the method.

Cell Data Sciences is now evaluating and refining the technology through selective collaborations, he said.

For example, a project with oncologists at the Stanford School of Medicine is part of the recent NIH funding.

That work, conducted with oncology researcher Ash Alizadeh, aims to "establish convincing proof of principle that [the] organocatalysts can be used to recover greater amounts of bimolecular signals from formalin-adducted RNA and DNA than literature-standard and commercial buffers and protocols," according to the grant abstract. It will also apply the catalyst method to clinically relevant nucleic acids in cell- and tissue-based FFPE specimens.

In addition, Orbai noted that the company is always interested in talking to other scientists and other companies about the specific problems they are facing with FFPE samples.

"We will also make our product generally available to the broader market," he added. The name hasn't been officially declared, but Orbai said the firm intends to have it commercialized "on the order of months."

"We really think that this is a true solution to this problem … [and that] a lot of the observed degradation of samples may happen upon extraction." 

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