Prime Editing Corrects GATA2 Deficiency in Patient Stem Cells

The double-strand break-free approach increased functional GATA2 alleles and improved the engraftment of edited blood stem cells in mice

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Prime editing repaired a disease-causing seven-base-pair GATA2 deletion in patient-derived CD34-positive blood stem and progenitor cells.
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After optimization, editing exceeded 70% and increased functional GATA2 alleles from 50% to as much as 77%, with higher GATA2 protein expression.
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Edited cells retained colony-forming capacity and achieved up to 2.73-fold greater engraftment than untreated cells in immunodeficient mice.
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Editing persisted in repopulating stem cells 16 weeks after transplantation, with no editing detected at the 20 highest-ranked predicted off-target sites.
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PASSIGE insertion of a larger corrective GATA2 sequence reached 4.6% of alleles, and the researchers said further optimization is needed.

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