The Advantages of Base and Prime Editing over Traditional CRISPR in the Treatment of Monogenic Diseases

CRISPR-Cas gene editing tools have revolutionized the field of biotechnology.Originally part of a bacterial immune system, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated proteins (Cas) can cleave specific DNA sequences that match the RNA sequence coded into the Cas protein.CRISPR has great potential for curing genetic diseases and cancers.However, many challenges must be overcome, including the risk of off-target cuts and their resulting consequences, on-target effects, adverse immune system reactions, the need for a double-stranded DNA break (DSB), and the need for a donor template to carry out homology-directed repair.Alternatively, base editing and prime editing are technologies that can edit genes without a DSB and donor template.There is also a reduced risk of off-target editing, which mitigates a significant safety concern.A key application of CRISPR and other gene editing technologies is curing monogenic diseases, which arise from mutations in a single gene.This makes them simpler to treat than other types of genetic diseases.Here, we present the principles of CRISPR, base editing, and prime editing, and discuss how they can be applied in a clinical setting to treat or cure monogenic diseases.