Novel technologies to isolate and analyze extrachromosomal dnas for diagnostic applications

Active Project Grant Awarded Last action

Award ID
R44GM151907
Recipient
Awarding agency
Obligated
$6,172,058

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 80% complete
Originally
Place of performance
San Carlos, CA 94070, USA

Award details come from USAspending.gov.

Description

Abstract
Extrachromosomal circular DNA (eccdna) elements are physically and topologically distinct components of eukaryotic genomes that can contribute to intercellular copy-number variation, environmental adaptations, and functional genomic diversity. Recently, high-throughput sequencing has made extensive genomic mapping of eccdna sequences possible. Notwithstanding this major advance, information regarding biogenesis of these circular dnas and causal connections between these DNA elements and human pathologies, remains extremely limited. The sequences, structure, and biological properties of eccdna molecules constitute a major knowledge GAP, information about which can lead to strategies targeting disease-specific eccdna structure and function. Eccdnas represent a large range of molecules (~100 BP to >1 MBP) and coexist with eccdnas found in normal somatic cells; isolating and characterizing different classes of eccdna comes with their own host of unique challenges. To address these knowledge gaps, methods that can directly interrogate all circular DNA species in the cell are critically needed. In this fasttrack sbir proposal, phinomics, INC. Is developing is developing an innovative urine-based test that will isolate eccdna molecules in an intact state suitable for next-generation sequencing and epigenetic characterization, and is complemented by a suite of biophysical and novel bioinformatic methods to identify and define these molecules. In phase i, phinomics will 1) demonstrate the capability of phinomics' proprietary technology to isolate comprehensive/unbiased eccdna repertoires (circulomes) from human cell lines; and 2) demonstrate the capability of phinomics' technology to robustly sequence, map, assemble, and informatically profile the isolated circulome. Upon meeting phase i go/no-go milestones, in phase II phinomics will 3) validate phinomics' technology as a molecular platform for bladder cancer diagnostic applications; 4) extend the application of phinomics' technologies to biological fluid samples; and 5) develop a PCR test to detect circular DNA species in non-muscle invasive bladder cancer to enable clia certification. Preliminary data has begun to illuminate the circulome in normal somatic cell lines and tissues, glioblastoma tumor samples, and plasma, potentiating the use of eccdna as a valuable biomarker in both solid- and liquid- biopsy applications. Surveillance based on eccdna biomarkers is aimed at a minimally invasive strategy to determine the immune response to therapies, predict recurrence likelihood, and monitor residual disease.

Transactions

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Amendment $0
Amendment $1,084,044
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Amendment $1,128,400
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Amendment $331,563
Original award $331,563
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Quick answers

Who received award R44GM151907?

R44GM151907 was awarded to Phinomics Inc. by National Institute of General Medical Sciences (National Institutes of Health) on August 1, 2023.

How much is award R44GM151907 worth?

$6,172,058 has been obligated on R44GM151907.

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