Liver biopsy confirms precise and efficient correction of SERPINA1 after in vivo Base Editing in a Patient with Alpha-1 Antitrypsin Deficiency.

In a 66-year-old man with PI*ZZ SERPINA1 alpha-1 antitrypsin deficiency, liver biopsy 10 weeks after in vivo base editing showed 54–57% correction of the PI*ZZ allele.

• Why it matters: Direct proof of hepatic gene correction is needed for AATD, where the PI*ZZ variant drives liver disease and low circulating AAT, but prior evidence has lacked biopsy-based confirmation.
• What they did: Within the YOLT-202 phase I/Ia trial, liver tissue was analyzed by Sanger and Illumina sequencing for PI*ZZ correction, including bystander and off-target editing, and AAT function was tracked by elastase inhibition.
• The result: Biopsy found no hepatic inflammation and no detectable off-target signals, while serum AAT levels and elastase inhibition activity were sustained after a transient transaminase rise.

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