Stabilization Of Cell-Free RNA In Plasma For Noninvasive Diagnosis And Prognosis

By M. R. Fernando, S. Norton and W. L. Ryan, Streck, Inc.

The discovery of the presence of cell-free nucleic acids in blood (1) and subsequent demonstrations that cell-free nucleic acids were elevated in certain disease conditions (2) suggested the usefulness of cell-free nucleic acids in non-invasive diagnosis and prognosis. The clinical utility of cell-free mRNA in blood as diagnostic and prognostic markers was first demonstrated in cancer patients (3). The presence of fetal cell-free mRNA in maternal blood was initially reported in 2000 by Poon et al. (4). Following this discovery many other clinically important fetal/placental cell-free mRNA molecules were found to be present in maternal blood. These discoveries have presented us with opportunities to develop non-invasive diagnostic and prognostic tools based on cell-free RNA. Due to its labile nature, there are inherent disadvantages of using cell-free mRNA in blood as biomarkers. Since plasma is rich in nucleases, cell-free mRNA tends to degrade during sample handling and processing. Another disadvantage is the release of non-target background RNA from blood cells during sample processing and storage. This kind of background increase hampers the detection of rare mRNA targets.