Cell-based interventions in utero: time to reconsider.

Abstract

In 1999, the NIH Recombinant DNA Advisory Committee held a Gene Therapy Policy Conference on in utero gene transfer (NIH, 1999) and determined that it would be premature to undertake in utero gene transfer research in humans (RAC, 1999). Much has happened since then. Gene transfer research enrolling infants and very young children as patient-subjects has had results both beneficial and harmful in several conditions (Hacein-Bey-Abina et al., 2003; Aiuti et al., 2012; Corrigan-Curay et al., 2012). Some fetal surgical interventions have become accepted (Adzick et al., 2011). And much has been learned about the immune system and how pregnancy influences immune response. We now know a lot more about how much more there is to learn. Researchers in cell- and gene-based interventions are eager to move to human trials in order to continue the learning process. Yet funders and oversight bodies are reluctant to support cell-based intervention research in human fetuses. In this commentary we address probable reasons for this hesitancy, reasons to move forward with caution, and issues to address in planning first-in-human (FIH) trials of cell-based interventions in utero.