Clinical Scorecard: Liver Gene Editing Corrects SERPINA1 Variant in One Patient With AATD

At a Glance

Key Highlights

• A single 35 mg infusion of investigational YOLT-202 was followed by liver biopsy at 10 weeks.
• The pathogenic SERPINA1 variant was corrected in 54% of alleles by Sanger sequencing and 57% by Illumina sequencing.
• No unintended changes were detected at nearby DNA positions or at the predicted off-target sites examined.
• Circulating AAT increased from 0.15 g/L before treatment to 0.7 g/L at 10 weeks; functional testing showed elastase-inhibiting activity.
• Transient liver enzyme elevations after infusion normalized within two weeks. Biopsy showed mild portal inflammation and fibrosis, residual misfolded AAT aggregates in relatively few hepatocytes, and no significant active liver injury.

Guideline-Based Recommendations

Diagnosis

Management

Monitoring & Follow-up

• In this study, investigators assessed editing efficiency, predicted off-target sites, liver histology, circulating AAT levels, and liver enzymes.

Risks

• Transient liver enzyme elevations occurred shortly after infusion and normalized within two weeks.
• Biopsy showed mild portal inflammation and fibrosis; no significant active liver injury was observed.

Patient & Prescribing Data

One 66-year-old male patient with severe Pi*ZZ AATD received treatment in an early-phase clinical trial.

YOLT-202, an investigational adenine base-editing therapy delivered by LNP, was administered intravenously as a single 35 mg infusion. At 10 weeks, circulating AAT was 0.7 g/L, above the commonly used therapeutic threshold of 0.57 g/L, and retained elastase-inhibiting function.

Clinical Best Practices

• The report describes early clinical evidence from one patient; larger clinical studies and longer follow-up are needed to determine whether molecular improvements provide lasting protection against liver and lung disease.

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