CSF-Seq: Whole-transcriptome Sequencing of Cerebrospinal Fluid Cell-free RNA for Molecular Profiling of Neurological Disease, Including Leptomeningeal Metastasis

Stanford scientists have developed CSF-Seq, a whole-transcriptome sequencing platform that reads cell-free RNA in cerebrospinal fluid to enable minimally invasive molecular profiling of neurological and neuro-oncologic disease, including leptomeningeal disease.

Many brain and central nervous system conditions are difficult to characterize at the molecular level because tissue is rarely accessible. This gap is especially acute in leptomeningeal disease, a rapidly fatal spread of cancer into the fluid surrounding the brain and spinal cord, where the current diagnostic standards of MRI and CSF cytology frequently miss disease and reveal little about its underlying biology. The result is delayed diagnosis, limited ability to predict which patients will progress quickly, and few tools to track disease over time.

CSF-Seq addresses this by capturing the entire transcriptome from the small amounts of fragmented, low-abundance RNA that circulate freely in cerebrospinal fluid, a sample type that had previously resisted broad molecular profiling. Using an optimized workflow for sample handling, RNA extraction, and deep sequencing, the platform produces reproducible molecular profiles from routinely collected CSF and reliably distinguishes leptomeningeal disease from other cancers and from non-cancer conditions. These profiles remain consistent regardless of how the fluid is collected or where it is processed, and the platform yields a prognostic signature that flags patients at highest risk of rapid progression, independent of standard clinical measures. This gives clinicians a minimally invasive tool to support earlier diagnosis, risk stratification, and longitudinal monitoring across leptomeningeal disease and a broad range of other CNS conditions where CSF is accessible.

Stage of Development
Proof of Concept