Head of Reprogramming/Stem Cell Biology Colossal Biosciences Boston, Massachusetts, United States
Abstract: Pioneer pluripotency transcription factors OCT4 and SOX2 drive reprogramming of somatic cells into stem cells capable of differentiating into any other type of cell. Recent work has shown that engineering of SOX2 can enhance reprogramming outcomes in multiple species including humans, mice, monkeys, cows, and pigs. Here we demonstrate that more radical engineering of both SOX2 and OCT4 using machine-learning-driven protein engineering approaches can enhance reprogramming outcomes beyond the state of the art. We show that engineering both OCT4 and SOX2 enhance reprogramming of mouse, antelope, and elephant somatic cells and we characterize the improvements in both reprogramming efficiency and reprogramming to a more naïve state. This work is part of a larger effort to design species-agnostic improvements to these proteins to reprogram somatic cells from non-model organisms to a fully naïve state for species conservation and de-extinction.
