Origin Genomics has announced initial preclinical results from OG-101, its BRCA1 gene-correction research programme. The company screened three prime-editor architectures with two pairs of three epegRNA designs targeting opposite strands of DNA around the correction site and optimised delivery conditions to correct a pathogenic BRCA1 splice-site mutation in a human breast cancer cell model.
The program advances Origin’s mission of therapeutic germline gene correction: correcting inherited disease mutations at the embryo stage, before birth. For BRCA1, the long-term goal is to prevent the elevated hereditary breast and ovarian cancer risk associated with the mutation.
Key findings and next steps include targeted correction, with up to 25.5 percentage points of correction above non-targeting control background. Also, up to 25.2% of analysed sequencing reads were cleanly corrected. Amplicon sequencing demonstrated conversion of the BRCA1 mutant allele towards WT sequence across all three prime-editor conditions: 93–96% of corrected reads contained no additional local changes under the analysis criteria.
Origin is moving forward with studies in induced pluripotent stem cells (iPSCs) and donated patient embryos carrying the same mutation through its IRB-approved preclinical research programme.
The findings establish an initial correction benchmark. Each reported condition was represented by a single sequencing library; additional independent validation will assess consistency and further optimisations will be made to refine correction efficiency and overall favourable outcome.
The next studies will measure correction efficiency, specificity, mosaicism, and genomic integrity in relevant developmental contexts. All embryo studies are conducted under independent ethics oversight for research only.