Jessica Ferrie

What are the advantages and disadvantages of base and prime editing over traditional CRISPR in the treatment of monogenic diseases?

Started May 25, 2023

Abstract or project description

CRISPR-Cas gene editing tools have revolutionized the field of biotechnology. Originally part of a bacterial immune system, Clustered Regularly Interspaced Short Palindromic Repeats and their associated proteins can be used to cut specific DNA sequences that match the RNA sequence coded into the Cas protein. CRISPR has great potential for curing genetic diseases and cancers. However, there are many challenges that have yet to be overcome before many more can be cured. These include the risk of off-target cuts and their resulting consequences, negative immune system reactions, the need for a double-stranded DNA break, and the need for a donor template in order to carry out homology-directed repair, the type of DNA repair required to correct a genetic mutation. Base editing and prime editing are emerging technologies that can edit genes but don’t require double-stranded DNA cleavage and a donor template. There is also a reduced risk of off-target editing, which mitigates a major safety concern. A drawback with base editing is that it can only convert a purine into another purine and a pyrimidine into another pyrimidine, not a purine into a pyrimidine or vice versa, which is a significant limitation. One of the most exciting applications of CRISPR and other gene editing technologies is the curing of monogenic diseases. Monogenic diseases are genetic diseases that arise from a mutation in a single gene. This makes them simpler to treat than diseases resulting from mutations in multiple genes, and because some of the most common genetic diseases are monogenic, monogenic diseases are of great interest. The purpose of this paper is to 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.