Blue Sky Science: What is gene editing?

Ed Williams

44

What is gene editing?

Gene editing involves changing the sequence of letters in the DNA. Researchers like to edit genes so they can understand the function of them, particularly genes that relate to various types of disorders that physicians have seen in the clinic. We can use this information to generate new hypotheses of how genes influence diseases.

Historically, editing the genome has been difficult. A number of editing technologies go into cells and essentially use “genetic scissors” to cut up the DNA. Once you introduce a cut into the genome, repair processes will try to repair that break. This repair often occurs in imprecise ways that could potentially cause errors and mutations.

Instead, you could take advantage of those repair processes to have the genome incorporate a foreign piece of DNA that has the letters that you want to be inserted.

Such editing has been done in human cells for the last 15-20 years using a set of proteins called nucleases. Nucleases are engineered proteins that cut DNA.

Recently, the Cas9 nuclease, part of the CRISPR system, has really accelerated the pace of editing throughout biology and engineering.

To give you a frame of reference, about 10 years ago when I started my graduate work and postdoctoral work, it cost about $50,000 to make only one precise cut in the genome. Attaining high precision was challenging: essentially finding a needle in a haystack, meaning editing one stretch of letters among three billion letters in the human genome. Understandably that was hard, and it took a lot of work to engineer the nucleases.

In the years since then, with the advent of the CRISPR system, a component called a guide RNA is used to attain precise editing. It’s easy to make the guide RNA and this enables us to easily go after multiple parts of the genome at once. These components can be made very quickly on the order of a few dollars rather than thousands of dollars, making the technology more accessible for research.