Spatiotemporal Delivery of CRISPR/Cas9 Genome Editing Machinery Using Stimuli‐Responsive Vehicles

Abstract Recent innovations in genome editing have enabled the precise manipulation of the genetic information of mammalians, and benefitted the development of next‐generation gene therapy. Despite these advances, several barriers to the clinical translation of genome editing remain, including the intracellular delivery of genome editing machinery, and the risk of off‐target editing effect. Here, we review the recent advance of spatiotemporal delivery of CRISPR/Cas9 genome editing machinery, which is composed of programmable Cas9 nuclease and a single‐guide RNA (sgRNA) using stimuli‐responsive nanoparticles. We discuss the specific chemistries that have been used for controlled Cas9/sgRNA delivery and intracellular release in the presence of endogenous or external signals. These methodologies can leverage biological signals found locally within disease cells, or exogenous signals administrated with spatiotemporal control, through which an improved genome editing could be achieved. We also discuss the future in exploiting these approaches for fundamental biomedical applications and therapeutic genome editing.