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UCSD Researchers Win Grant to Develop Extracellular RNA Biomarker Panel for Glioma

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NEW YORK (GenomeWeb) – Researchers at the University of California, San Diego have been awarded funding to develop a panel of extracellular RNA biomarkers for non-invasive glioma brain tumor diagnosis.

The research is being conducted in the lab of Bob Carter, a professor and chief of neurosurgery at UC San Diego Health System and a researcher in UCSD's Center for Theoretical and Applied Neuro-Oncology.

The two-year grant, totaling $984,048, is the second phase of funding for this research awarded by the National Institutes of Health's National Center of Advancing Translational Sciences.

In 2013, the NIH Common Fund began providing support for 30 exRNA research projects, and NCATS currently administers 18 of those projects, including Carter's. 

Today, NCATS officially announced the second round of exRNA research funding, noting specific focus areas including Alzheimer’s disease, multiple sclerosis, kidney disease, brain injury, pregnancy complications, heart disease, heart attack, and stroke, as well as liver, stomach, and brain cancers.

The glioma project involves examining cerebrospinal fluid and blood from patients with brain tumors to search for vesicle-packaged extracellular RNA signatures that might inform diagnosis or tumor monitoring, Carter told GenomeWeb.

The funding supports investigating different competing technologies for exRNA biomarker detection, including qPCR, digital PCR, and exome sequencing.

Among these, Carter said his group has considered different platforms for digital PCR and settled on the Bio-Rad Droplet Digital PCR system based on cost and throughput. He said the group is "very intrigued" with the RainDance system but has not used it.

Collaborative exRNA space

UCSD's Carter is an investigator in the Extracellular RNA Communication Consortium, a group established in 2013 via the NIH Common Fund to address critical issues in exRNA research. 

Progress on the brain tumor work was recently outlined in a review of extracellular RNA biomarkers published by the consortium in a special issue of the Journal of Extracellular Vesicles.

The consortium, with Carter as co-author, also published a preliminary assessment of extracellular RNA sample preparation and detection techniques in the JEV special issue, highlighting growth and challenges in the field, particularly a current need for standardization of methods.

Carter also co-authored a Nature Cell Biology paper in 2008 that initially described microvesicles released from gliomas and highlighted their potential use as diagnostic biomarkers.

The first author on that study was Johan Skog, then affiliated with the departments of neurology and radiology at Harvard Medical Center. Skog is now founding scientist and chief scientific officer at Exosome Diagnostics (ExDx).

"We've worked really closely with ExDx over the years, and they made available to us some of their test kits in partnership with Qiagen early on," Carter noted.

Data from that collaboration, in conjunction with funds from a private, non-profit foundation investing in brain cancer research called ABC2, is expected to be published in the near future, Carter said.

Meanwhile, ExDx announced last week that it will use $44.7 million raised in its Series B financing round to launch liquid biopsy cancer tests this year.

Carter is also collaborating on a project with Ralph Weissleder's lab at Harvard, described recently in Nature Communications, to develop a microfluidic device using exosome-binding magnetic nanoparticles that pluck vesicles from samples, although this technology is not the focus of the recent glioma grant.

Carter further noted that his group at UCSD has teamed up with Oregon Health Sciences and the Translational Genomics Research Institute to research cerebrospinal fluid exRNA specifically. The sister institutions will look at the ability of CSF exosomes to provide material for sequencing platforms, as well as for mRNA and microRNA arrays, Carter said.

Each site has a disease focus, with OHSU interested in Parkinson's and Alzheimer's, UCSD investigating brain tumors, and TGen looking at brain trauma and subarachnoid hemorrhage.

The Carter lab is also working with an organization called the Scintillon Institute to develop nano-FACS for exosomes based on the principle that different markers may be expressed on the surfaces of exosomes from different bodily sources.

Finally, the group is working with San Diego-based Regulus Therapeutics to develop a qPCR microRNA expression array for its preliminary brain tumor signature, Carter said.

That firm has been considering spinning off its microMarkers microRNA research division into a separate company to develop and market clinical assays. This could include a microMarkers project on brain tumor biomarkers funded by ABC2 and conducted in collaboration with UCSD, Regulus told GenomeWeb last year.

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