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Donor-Derived Cell-Free DNA: An Accurate, Precise, and Dynamic Biomarker for Improved Management of Solid Organ Transplant Patients

Friday, 6 October 2017 at 14:00

Add to Calendar ▼2017-10-06 14:00:002017-10-06 15:00:00Europe/LondonDonor-Derived Cell-Free DNA: An Accurate, Precise, and Dynamic Biomarker for Improved Management of Solid Organ Transplant PatientsLiquid Biopsies and Minimally-Invasive Diagnostics 2017 in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com

Cell-free DNA (cfDNA) has been described as a biomarker for prenatal testing, cancer, and organ transplantation, each of which present different clinical and technological challenges. cfDNA circulating in the plasma of transplant recipients represents a mixture of recipient cfDNA and residual nucleosome-protected genomic regions released from dying cells of the allograft (“transgenome”). The genomes of the organ donor and allograft recipient are distinguishable by sequencing total cfDNA from the plasma. A clinical-grade cfDNA NextGen sequencing (NGS) assay was developed to monitor the levels of the “transgenome”, enabling assessment of the allograft status of transplant recipients with high confidence analytical validation. The NGS-based assay does not require testing of genetic material from the donor or recipient thereby simplifying the testing of transplants with cadaveric donors.  Longitudinal samples from heart, lung and kidney transplant patients had higher dd-cfDNA levels at biopsy-confirmed rejection which were reduced following adjustments to immunosuppressive therapy in clinical validation studies. Serial assessment of dd cfDNA provides a measure of both the amount and kinetics of dying allograft cells, information clinicians may use to inform clinical utility.