Highly Efficient and Precise Gene Editing in Blood Stem and Progenitor Cells Using SaCas9 and AsCas12a Ultra

SaCas9 achieved higher efficiencies in correcting the sickle mutation compared to SpCas9.

• SaCas9 showed greater efficiency in targeting the BCL11A erythroid enhancer than SpCas9.
• AsCas12a demonstrated superior editing at the HBG promoter, leading to higher levels of fetal hemoglobin.
• Both SaCas9 and AsCas12a had reduced off-target and unintended on-target editing compared to SpCas9.
• The persistence of large deletions from BCL11A enhancer editing was assessed after 20 weeks in NBSGW mice.
• SaCas9 and AsCas12a may serve as promising alternatives to SpCas9 for gene editing in therapeutic applications.

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