Periodic Reporting for period 1 - NIPCT (Non-invasive prenatal diagnostics – Isolation of circulating trophoblast cells using a malaria protein)
Reporting period: 2020-01-01 to 2021-06-30
During the last decade, capturing circulating trophoblast cells in the maternal circulation has been of utmost interest as the targeted cells provide a noninvasive source of fetal DNA valuable for prenatal screening and diagnostics. Noninvasive prenatal testing has become desirable, as it allows for molecular analysis of the fetal genome with only limited maternal side effects. However, due to the scarcity of the circulating trophoblast cells, the majority of isolation strategies still struggle with low sensitivities and specificities, which impedes the possibility of applying circulating trophoblast cells as a method for prenatal testing. This project aimed to implement an rVAR2-based capture method for retrieval of circulating trophoblast cells. The rVAR2-based capture method utilizes on an anchor protein, VAR2CSA, expressed by the malaria parasite P. falciparum. VAR2CSA normally mediates binding of malaria-infected erythrocytes in the placenta during pregnancy-associated infections. A recombinant form of this anchor protein (rVAR2) also allows for binding to the trophoblast layer in the placenta. In this project, we aimed to investigate whether the specific rVAR2 binding could be utilized for the capture and detection of circulating trophoblasts. We showed proof of concept by spiking in BeWo cells of placental origin into blood samples and further we demonstrated that we could capture placental cells from blood samples of pregnant women. The technology holds the promise to be developed to a non-invasive fetal diagnostic tool.