Hematopoietic stem cell gene editing and expansion: State-of-the-art technologies and recent applications.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for a range of hematological diseases, from leukemias to immunodeficiencies and anemias. The aim in using HSCT is to replace a patient's dysfunctional blood system with a functional one by transplanting healthy hematopoietic stem cells (HSCs). HSCs may be collected from a healthy donor (for allogeneic HSCT) or from the patient for genetic correction (for autologous HSCT gene therapies). Despite the curative potential of HSCT, several hurdles to its wider and safer use remain, including how to efficiently genetically correct HSCs and how to increase donor HSC numbers to improve the donor pool. In recent years, the development of state-of-the-art technologies, such as Cas9-AAV6 technologies and identification of the small molecule HSC agonist UM171, have accelerated progress in HSC gene editing and expansion. These translational research efforts were the focus of the Spring 2021 International Society for Experimental Hematology (ISEH) webinar. Here we present a summary and discussion of the implications of these new approaches to improve HSC-based therapy.

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Déclaration de conflit d'intérêts

Conflict of interest disclosure Dr. M Porteus has equity and serves on the scientific advisory board of CRISPR Therapeutics and Allogene Therapeutics. However, none of these companies had input into the design, execution, interpretation, or publication of the work in this article. All other authors do not declare any competing interests.