Use Of Cell-free Nucleic Acids Research Articles

Cell-free nucleic acids as biomarkers in dialyzed patients

In this review, we discuss the origin, possible biological meaning, quantitative and qualitative changes in the concentrations of cell-free nucleic acids in human circulation with regard to renal failure and the process of dialysis. We focus on the inflammatory response and apoptosis known to be in close relationship not only with hemodialysis but also with different comorbidities frequently detected in hemodialyzed patients. Hemodialysis itself is able to promote the changes in the quantity and quality of circulating nucleic acid pool, but large spectrum of comorbidities in hemodialyzed subjects can further complicate the interpretations of results of cell-free nucleic acid analysis. Such analysis can provide additional information about the patient prognosis and monitor some aspects of comorbidity development. Recently, it has been shown that the analysis of cell-free nucleic acids may also be worthy in patients on peritoneal dialysis because the cell-free nucleic acids may also be detected in overnight effluents and their examination can be informative with regard to the functional state of the patient's peritoneum. We summarize what is recently known about the use of cell-free nucleic acids as biomarkers in patients with renal failure not only in hemodialysis but also in peritoneal dialysis and we describe the future perspectives in this field.

Transplantation Monitoring by Plasma DNA Sequencing

Over the past 15 years, there has been increasing interest in the use of cell-free nucleic acids in plasma for molecular diagnostics, especially for cancer detection and prenatal diagnosis. In 1998, Lo et al. showed that donor-derived DNA sequences could be detected in the plasma of transplant recipients (1). This group further showed that different transplanted organs—e.g., the heart, liver, and kidney—appeared to release different amounts of DNA into the plasma, probably relating to the size of the organ (2). Furthermore, details in the design of the molecular assay have been shown to have important implications for detecting circulating donor-derived DNA. For example, the use of a detection target, DYS14 (1,3), which is a member of a multicopy Y chromosome–specific gene, TSPY1 3 (testis specific protein, Y-linked 1), has produced a higher sensitivity in detecting circulating donor-derived DNA than when the single-copy gene SRY (sex-determining region Y) is used (2). As cell death is generally accepted to be an important reason for the release of DNA into the plasma, Lo et al. further hypothesized that the measurement of donor-derived DNA in the plasma of transplant recipients might be used for monitoring graft rejection (1). This hypothesis has subsequently been shown to be correct by a number of independent workers (4),(5). The usefulness of this strategy depends, however, on the ability to design molecular assays that allow the detection of donor-specific DNA sequences. Most workers in this field have thus far used …

Insights into fetal and neonatal development through analysis of cell-free RNA in body fluids

The use of cell-free nucleic acids in the circulation of pregnant women for noninvasive prenatal diagnosis is arguably one of the hottest current topics in prenatal medicine. Between 1997 and the present era this field has gone from basic research to clinical application for diagnosis of fetal gender and Rhesus D status. Over the next few years it is likely that noninvasive prenatal diagnosis for Down syndrome will also be possible. Here we summarize current and future clinical applications of analyzing cell-free fetal DNA and RNA in both maternal and neonatal body fluids, including maternal plasma, serum, whole blood, amniotic fluid, and neonatal saliva. We describe methods to evaluate normal and abnormal fetal and neonatal development using gene expression microarrays. We also discuss the ways in which differentially-regulated gene lists can advance knowledge of both fetal and neonatal biology, as well as suggest novel possibilities for fetal and neonatal treatment.