AUTHOR=Wolff Jonas Holst , Mikkelsen Jacob Giehm 

TITLE=Prime editing in hematopoietic stem cells—From ex vivo to in vivo CRISPR-based treatment of blood disorders

JOURNAL=Frontiers in Genome Editing

VOLUME=5

YEAR=2023

URL=https://www.frontiersin.org/journals/genome-editing/articles/10.3389/fgeed.2023.1148650

DOI=10.3389/fgeed.2023.1148650

ISSN=2673-3439

ABSTRACT=<p>Prime editing of human hematopoietic stem cells has the potential to become a safe and efficient way of treating diseases of the blood directly in patients. By allowing site-targeted gene intervention without homology-directed repair donor templates and DNA double-stranded breaks, the invention of prime editing fuels the exploration of alternatives to conventional recombination-based <italic>ex vivo</italic> genome editing of hematopoietic stem cells. Prime editing is as close as we get today to a true genome editing drug that does not require a separate DNA donor. However, to adapt the technology to perform <italic>in vivo</italic> gene correction, key challenges remain to be solved, such as identifying effective prime editing guide RNAs for clinical targets as well as developing efficient vehicles to deliver prime editors to stem cells <italic>in vivo</italic>. In this review, we summarize the current progress in delivery of prime editors both <italic>in vitro</italic> and <italic>in vivo</italic> and discuss future challenges that need to be adressed to allow <italic>in vivo</italic> prime editing as a cure for blood disorders.</p>