Miniature editors play a crucial role in genomic editing and gene therapy, particularly in addressing human genetic diseases caused by base mutations. Currently, approximately 60% of known human genetic diseases are attributed to base mutations. Traditional CRISPR technology poses risks such as double-stranded DNA breaks, whereas base editors can efficiently convert single bases at target sites without such breaks. Currently, the most widely used base editors include:
The efficiency and tissue specificity of base editor delivery are critical for the success of gene therapy. Adeno-associated viruses (AAVs) have become the primary delivery tool for gene therapy due to their high efficiency and tissue specificity. However, base editors mediated by SpCas9 nickase (D10A) are too large to be packaged into AAVs, which have a packaging limit of approximately 4.7 kb. Thus, developing more compact and efficient base editors is essential.