The specific DNA sequence targeted by this gene-editing therapy is the same in nearly all people studied, regardless of ancestry, meaning the same treatment could potentially work for most people without needing to be customized.
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 the conservation of the PCSK9 gRNA target site across ancestries is consistent across all major human populations and correlates with similar editing efficiency and safety outcomes.
A systematic review and meta-analysis of all published genomic datasets from global populations (e.g., gnomAD, 1000 Genomes, HapMap) assessing the frequency of the 20-bp PCSK9 target sequence across continental ancestries, combined with functional validation studies of editing efficiency in cells from diverse genetic backgrounds.
Whether VERVE-102 achieves comparable PCSK9 editing and LDL-C reduction in individuals of African, Asian, and European ancestry.
A multicenter, double-blind RCT of 300 participants with heterozygous familial hypercholesterolemia, stratified by ancestry (100 each of European, African, and East Asian descent), randomized to VERVE-102 or placebo, measuring on-target editing efficiency by deep sequencing and LDL-C reduction at 24 weeks.
Whether individuals from different ancestral backgrounds who receive VERVE-102 show similar rates of sustained LDL-C reduction and adverse events over time.
A prospective cohort study following 1,000 individuals with heterozygous familial hypercholesterolemia from diverse ancestries who receive VERVE-102, tracking editing efficiency, LDL-C levels, and safety events annually for 5 years, with ancestry determined by genetic ancestry markers.
Whether the frequency of the target sequence varies significantly between populations and whether this correlates with baseline PCSK9 levels.
A cross-sectional analysis of 5,000 individuals from 10 global populations, measuring the frequency of the 20-bp PCSK9 target sequence via genotyping and correlating it with baseline serum PCSK9 and LDL-C levels.
Whether rare genetic variants near the target site in underrepresented populations affect VERVE-102 binding or editing efficiency.
Detailed reporting of 5–10 individuals from underrepresented ancestries (e.g., Indigenous, Oceanic) who received VERVE-102 and underwent deep sequencing to identify variants within or near the 20-bp target region that might alter editing efficiency.