adenine base editor mRNA

Adenine base editor (ABE) mRNA is a gene-editing therapeutic modality consisting of messenger RNA that encodes an adenine base editor protein. ABEs are engineered chimeric proteins, typically comprising a catalytically impaired CRISPR-Cas9 (such as a nickase) fused to a deoxyadenosine deaminase enzyme (e.g., an evolved TadA). When delivered as mRNA, the cell's translation machinery produces the ABE protein, which, guided by a co-delivered guide RNA (gRNA), performs precise A-to-G (T-to-C) point mutations at specific genomic loci without creating double-strand breaks. In the context of sickle cell disease (SCD), this technology is used to convert the pathogenic mutation in the $\beta$-globin gene (HBB) into a benign naturally occurring variant, such as Makassar hemoglobin (HbG), or to disrupt regulatory elements like the BCL11A erythroid enhancer to induce fetal hemoglobin production.

Other names

adenine base editor-encoded mRNAmRNA-encoded adenine base editor