Gene Editing Shows Promise for Alpha-1 Antitrypsin Deficiency

First liver biopsy following in vivo base editing confirms precise correction of the disease-causing mutation in Pi*ZZ AATD patient

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A 66-year-old man with Pi*ZZ alpha-1 antitrypsin deficiency received a single intravenous infusion of the investigational base-editing therapy YOLT-202.
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Ten weeks after treatment, liver biopsy showed correction of 54% of targeted SERPINA1 alleles by Sanger sequencing and 57% by Illumina sequencing.
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Testing found no detectable unintended editing at nearby DNA positions or predicted off-target sites.
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Circulating alpha-1 antitrypsin rose from 0.15 g/L before treatment to 0.7 g/L at 10 weeks, and functional testing confirmed elastase inhibition.
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Larger studies and longer follow-up are needed to determine whether the molecular improvements provide lasting protection against liver and lung disease.

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