Editing human hematopoietic stem cells: advances and challenges

Senthil Velan Bhoopalan; Jonathan S Yen; Rachel M Levine; Akshay Sharma

doi:10.1016/j.jcyt.2022.08.003

Editing human hematopoietic stem cells: advances and challenges

Cytotherapy. 2023 Mar;25(3):261-269. doi: 10.1016/j.jcyt.2022.08.003. Epub 2022 Sep 17.

Authors

Senthil Velan Bhoopalan¹, Jonathan S Yen², Rachel M Levine², Akshay Sharma³

Affiliations

¹ Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
² Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
³ Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. Electronic address: akshay.sharma@stjude.org.

PMID: 36123234
DOI: 10.1016/j.jcyt.2022.08.003

Abstract

Genome editing of hematopoietic stem and progenitor cells is being developed for the treatment of several inherited disorders of the hematopoietic system. The adaptation of CRISPR-Cas9-based technologies to make precise changes to the genome, and developments in altering the specificity and efficiency, and improving the delivery of nucleases to target cells have led to several breakthroughs. Many clinical trials are ongoing, and several pre-clinical models have been reported that would allow these genetic therapies to one day offer a potential cure to patients with diseases where limited options currently exist. However, there remain several challenges with respect to establishing safety, expanding accessibility and improving the manufacturing processes of these therapeutic products. This review focuses on some of the recent advances in the field of genome editing of hematopoietic stem and progenitor cells and illustrates the ongoing challenges.

Trial registration: ClinicalTrials.gov NCT03745287 NCT04443907.

Keywords: CRISPR-Cas9; hematopoietic stem cells; severe congenital neutropenia; sickle cell disease.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

CRISPR-Cas Systems* / genetics
Gene Editing / methods
Genetic Therapy / methods
Hematopoietic Stem Cells*
Humans

Associated data

ClinicalTrials.gov/NCT03745287
ClinicalTrials.gov/NCT04443907