Researchers review how two such experiments—the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology—have fundamentally reshaped our approach to biomedical research, stem cell biology, and human genetics. They highlight the previous knowledge that iPSC and CRISPR/Cas9 technologies were built on as this groundwork demonstrated the need for solutions and the benefits that these technologies provided and set the stage for their success.

Despite the obvious advances that have been made as a result of iPSC and editing technologies, several challenges remain. A key limitation remains that human cells prefer to choose the imprecise NHEJ pathway to repair a DSB rather than use the more precise homologous DNA repair pathway using an exogenous repair template. Due to this pathway choice, editing events often result in NHEJ-mediated insertions and deletions at the DSB rather than the intended homology-mediated modification.