Ex vivo HSC gene therapy requires collection and purification of the patient’s HSCs and in vitro manipulation of the stem cells to induce proliferation, followed by gene therapy and finally transplantation. Typically, cytoreductive conditioning of the patient is required to make room for engrafting stem cells—manipulations that increase the costs of treatment and require facilities capable of performing stem cell transplants. In contrast, in vivo gene editing potentially could be performed by simple infusion of a suitable vector to deliver a prime editor to HSCs within the bone marrow, bypassing the need for stem cell transplantation and allowing for greater dissemination of gene therapy treatments globally. Figure created with BioRender.com.