The abstract is read at the publisher; the summary is JClub's.
Adenine base editing corrected the recurrent STAT1 p.T385M gain-of-function mutation with >90% efficiency in patient T cells and HSCs, restoring STAT1 signaling and immune function.
- Why it matters: STAT1 GOF IEI is dominantly inherited and linked to chronic candidiasis, autoimmunity, severe opportunistic infections, and malignancy risk, while HSCT carries higher morbidity and mortality than other IEIs.
- What they did: The team tested CRISPR/Cas homology-directed repair in STAT1 GOF model lines, primary T cells, and patient-derived HSCs, then used adenine base editing to target p.T385M and measured STAT1 expression, phosphorylation, interferon-stimulated gene activity (OAS1), and IL-17 production.
- The result: Base editing increased total STAT1 expression (P< .0217), STAT1 phosphorylation (P< .0056), OAS1 expression (P = .0005), and improved IL-17 production (P< .0001), with edited HSCs persisting at 16 weeks after engraftment in humanized immunodeficient mice.
The findingWhy it mattersWhat they didThe result
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