A gene therapy called YOLT-101 uses special nanoparticles to deliver gene-editing tools directly to liver cells, where it permanently changes the PCSK9 gene to reduce its activity.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether GalNAc-LNP delivered adenine base editors consistently achieve PCSK9 gene editing in human hepatocytes and whether editing efficiency correlates with PCSK9 and LDL-C reduction across studies.
A systematic review and meta-analysis of all published human studies using GalNAc-LNP base editors targeting PCSK9, pooling data on on-target editing efficiency (via NGS of liver tissue), PCSK9 reduction, and LDL-C reduction to determine correlation strength.
Whether YOLT-101 causes PCSK9 gene editing in human hepatocytes compared to placebo.
A double-blind, placebo-controlled trial of 50 adults with heterozygous familial hypercholesterolemia, randomized to YOLT-101 or placebo, with liver biopsy performed at 4 weeks to quantify A-to-G editing at the PCSK9 locus via deep sequencing and measure PCSK9 mRNA and protein levels.
Whether the degree of PCSK9 gene editing in liver tissue predicts the magnitude and durability of LDL-C reduction over time.
A prospective cohort study of 100 individuals treated with YOLT-101, with liver biopsy at 4, 12, and 52 weeks to quantify editing efficiency via NGS, and correlation with longitudinal LDL-C and PCSK9 measurements.
Whether individuals with minimal LDL-C reduction after YOLT-101 have lower rates of on-target editing in liver tissue compared to responders.
A case-control study comparing liver biopsy samples from 15 responders (≥50% LDL-C reduction) and 15 non-responders (<20% reduction) to quantify A-to-G editing efficiency at the PCSK9 target site via deep sequencing.
Whether individuals treated with YOLT-101 have detectable A-to-G editing in peripheral blood or liver tissue at a single time point.
A cross-sectional analysis of 50 individuals treated with YOLT-101, measuring A-to-G editing in plasma cell-free DNA and liver biopsy tissue (if available) at 4–8 weeks post-infusion to assess editing presence.