Gene editing of hematopoietic stem cells: applications and advances

Allogeneic hematopoietic stem cell transplantation remains the standard treatment for various hematologic genetic disorders resulting from single or multiple genes. However, this strategy is hindered by two main problems: failure to find a matching donor and the risk of graft-versus-host disease (GVHD) after transplantation. Recent advances in gene editing, particularly nucleases exemplified by clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) and related derivative tools, have overcome the limitations posed by the poor specificity of traditional gene modification techniques. A robust groundwork has been established for developing efficient, precise, and diverse gene editing strategies, facilitating the clinical application of ex vivo modified autologous hematopoietic stem cells (HSCs). In contrast, autologous HSC transplantation does not have the previously mentioned problems associated with allogeneic transplantation. Consequently, gene editing involving ex vivo genetic modification of HSCs and subsequent reinfusion in a single patient has emerged, with related research progressing from investigation into fundamental mechanisms and proof-of-concept studies to clinical trials.