cPRIME enables endogenous mapping of genetic variant effects at RNA level.

cPRIME enables endogenous mapping of genetic variant effects at RNA level, revealing that synonymous marker edits can alter RNA processing in diverse genomic contexts.

• Why it matters: Understanding the functional impact of genetic variants, especially VUS, is crucial for interpreting their roles in disease, including cancer, but current methods lack RNA-level assessment.
• What they did: The study developed cPRIME, a scalable approach using prime editing and cDNA readout to insert variants into endogenous loci and quantify their effects across different karyotypes and genomic sites.
• The result: cPRIME provides a platform for studying post-transcriptional consequences of variants within their genomic context, aiding the functional interpretation of RNA-altering variants in disease research.