The CRISPR-Cas9 technology, and the subsequent research-based innovations stemming from its discovery, integrate chemistry and evolution to program and re-program biology. David Liu at the Broad Institute has taken the basics of CRISPR and innovated the technology from cutting DNA to actually chemically swapping its component base pairs (Cytosine, Guanine, Adenine, and Thymine).
“The majority of human genetic diseases, which collectively affect hundreds of millions of people, are caused by single-letter (‘base’) changes on DNA. These single-letter swaps or ‘point mutations’ cause grievous diseases such as sickle-cell anemia, progeria, or muscular dystrophy. For many such diseases, correcting the DNA base from the pathogenic form back to the normal form is thought to offer a potential treatment or even a permanent cure. Towards this goal, our lab created molecular machines known as ‘base editors’ that directly correct point mutations in living cells and organisms.
“Through a combination of protein engineering and protein evolution, we developed two classes of base editors that together enable four kinds of base-to-base conversions at target positions in genomic DNA with high efficiency and few unwanted byproducts. The mutations that these base editors can correct collectively account for most known human pathogenic point mutations. Base editing has been used by many laboratories around the world in a wide range of organisms including bacteria, fungi, plants, fish, mammals, and even human embryos. We and others have integrated several of these developments to treat animal models of human genetic disease. “This short film overviews the history of base editing and introduces the concepts behind the technology to a general audience.” – Liu lab