Genome Editing of Pluripotent Stem Cells for Adoptive and Regenerative Cell Therapies

Abstract

The explosion of interest in CRISPR-Cas systems over recent years has delivered rapid advances in precision genome engineering technologies that hold enormous potential for application across the biotechnology sector. Within the cell therapy space, adoptive immunotherapies continue to lead the translation of increasingly sophisticated genetic engineering strategies toward clinical application. Although early focus was placed on engineering primary immune cells collected from patient blood, the democratization of these therapeutics will require the development of off-the-shelf allogeneic cell therapy products that can be manufactured at scale. Pluripotent stem cells (PSCs) represent an attractive substrate for such products, and many of the challenges that must be overcome to realize the application of PSCs in adoptive cell therapies are common with those holding back regenerative cell-replacement therapies. This article discusses how genome editing can overcome these challenges and highlights the potential of rapidly advancing second-generation technologies in the development of novel cell-based therapeutics.