Prime and base editing for blood disorders, mutation tracing for NASH target discovery and more

A pair of studies captured the preclinical performance of prime and base editing systems for ex vivo correction of mutations driving sickle cell disease and hemoglobin E β-thalassemia, respectively, without inducing double-stranded breaks or requiring donor DNA templates.

Prime Medicine Inc. (NASDAQ:PRME) co-founder David Liu and colleagues described in Nature Biomedical Engineering a one-time hematopoietic stem cell (HSC) prime-editing therapy for sickle cell disease (SCD). HSCs from SCD patients edited using the prime system and transplanted into mice resulted in an average of 42% engrafted human erythroblasts and reticulocytes containing at least one corrected HBB allele at 17 weeks, exceeding the levels predicted to be required for therapeutic benefit. The authors have filed patent applications for the approach via the Broad Institute...