Circulating cell-free DNA in the bloodstream holds the promise of non-invasive "liquid biopsies" for cancer diagnostics. Mutations that drive the growth and spread of tumors are present and detectable within this genetic pool despite being outnumbered by vast amounts of wild-type DNA. However, there are no single genetic biomarkers of cancer and so to be of practical use many possible mutations must be screened simultaneously. Current techniques lose the high sensitivity required for this needle-in-a-haystack search once multiple mutations are targeted. Lariat Biosciences is developing new technologies that break this trade-off between sensitivity and breadth, providing for the first tim the complete tools necessary to mine the bloodstream for clinically actionable signs of cancer. The Lariat technology pairs the exquisite sensitivity of emulsion digital PCR, capable of mutant quantitation at mutant-to-wild-type ratios of 1:105 to 1:106, with the ability to isolate and deepl characterize the detected mutant DNA afterwards. With orthogonal methods of DNA identification, the false positives that undermine the multiplexed sensitivity of current technique are eliminated. Lariat's initial product offering will be a comprehensive genetic screen for the common mutations in EGFR and KRAS, a nine-plex assay that will be useful for predicting patient response to tyrosine kinase inhibitor drugs and for monitoring emerging resistance to therapy.
Public Health Relevance Statement:
Public Health Relevance: Circulating cell-free DNA in the bloodstream holds the promise of noninvasive "liquid biopsies" for cancer diagnostics. Mutations that drive the growth and spread of tumors are present and detectable within this genetic pool despite being outnumbered by vast amounts of healthy wild- type DNA. Lariat Biosciences is developing new technologies that provide for the first time the complete tools necessary to mine the bloodstream for clinically actionable signs of cancer.
Project Terms:
aqueous; Biochemical; Biological Assay; Biopsy; Biotechnology; Blood; Blood Circulation; Businesses; Cancer Diagnostics; cancer therapy; Cell Separation; Clinical; clinical application; Clonality; Color; Complex; Confusion; Data; Detection; Development; Diagnostic Neoplasm Staging; digital; Disease; Disease Resistance; DNA; DNA amplification; DNA Sequence Alteration; Drug Monitoring; Drug resistance; Early treatment; Emulsions; Engineering; Epidermal Growth Factor Receptor; Equation; Fluorescence; Fluorescent Probes; Gel; Genes; Genetic; Genetic Fingerprintings; Genetic Markers; genetic profiling; Genetic Screening; genetic variant; Genotype; Grant; Growth; Heterogeneity; Human; human DNA; Hydrogels; Individual; KRAS2 gene; Liquid substance; Malignant Neoplasms; Methods; Microfluidic Microchips; Microfluidics; Mining; Monitor; mutant; Mutation; Needle biopsy procedure; Needles; new technology; novel; novel strategies; nucleic acid quantitation; Oils; particle; Patients; Performance; Phase; Polymers; Process; Protocols documentation; public health relevance; Reaction; Research; Residual Neoplasm; response; Sampling; Seeds; Services; Solutions; Somatic Mutation; Sorting - Cell Movement; Source; Specificity; Staging; Staining method; Stains; success; synthetic construct; Techniques; Technology; therapy resistant; Time; Tissues; tool; treatment response; tumor; Tyrosine Kinase Inhibitor