BASE EDITORS

The DNA is the foundation of variability. The different arrangements of four nitrogenous bases, thymine, adenine, guanine and cytosine, determine how cells function and what characteristics an orgamism possesses. An organism's genome contains millions of bases which code for proteins with a variety of functions. With a possible bases comes a million possible errors. Each base in the genome has a probability of being switched out for the wrong base due to mutations from UV radiation, errors during DNA replication and even mutagenic substances. Mutations that arise from changing single bases are called point mutations and these account for numerous genetic disorders muscular dystrophy, sickle-cell anemia, phenylketonuria etc. With the advent of CRISPR-Cas9 system, it is posisble to create double-stranded breaks that allow the integration of random sequences. This is useful in research settings where knockout mutations are the aim but for therapy, the traditional CRISPR/Cas9 machinery may only aggravate the disease. The need to change single nucleotides spurred the discovery of base editors. Base editors consist of inactive Cas9 scissors paired with a protein that catalyzes the desired base change. In order to circumvent potential revertion to the incorrect base by the cell's proof-reading machinery, the base editor creates a nick in the other strand of DNA. This marks that strand for correction, allowing the proof-reading machinery to integrate the correct complementary base.