Progress Toward Genetic Rescue of the Northern White Rhinoceros (Ceratotherium simum cottoni).

The northern white rhinoceros (NWR) is functionally extinct, with only two nonreproductive females remaining. However, because of the foresight of scientists, cryopreserved cells and reproductive tissues may aid in the recovery of this species. An ambitious program of natural and artificial gametes and in vitro embryo generation was first outlined in 2015, and many of the proposed steps have been achieved. Multiple induced pluripotent stem cell lines have been established, primordial germ cell-like cells have been generated, oocytes have been collected from the remaining females, blastocysts have been cryopreserved, and the closely related southern white rhinoceros (SWR) is being established as a surrogate. Recently, the first successful embryo transfer in SWR demonstrated that embryos can be generated by in vitro fertilization and cryopreserved. We explore progress to date in using advanced cellular technologies to save the NWR and highlight the necessary next steps to ensure a viable population for reintroduction. We roll out a holistic rescue approach for a charismatic megavertebrate that includes the most advanced cellular technologies, which can provide a blueprint for other critically endangered mammals. We also provide a detailed discussion of the remaining questions in such an upgraded conservation program.