WSJournal. Editing Our Genes, One Letter at a Time
Scientists at the Massachusetts Institute of Technology and Rockefeller and Harvard universities have found a new method of editing DNA with great precision. This and another new technique mean that scientists can now go into a cell, find a particular sequence in the genome and change that sequence by a single letter.
Just to get your mind around this feat, imagine taking about 5,000 different novels and reprinting them in normal font size on 23 very long cotton ribbons. Since each word takes up about half an inch, the ribbons, placed end to end, would stretch for roughly three million miles—120 times around the world. But to be a bit more realistic, twist and tangle the ribbons so much that they only go around the planet once.
One of the books written on your ribbons is "A Tale of Two Cities," but you don't even know which ribbon it is on, let alone where on that ribbon. Your task is to find the clauses "It was the beast of times, it was the worst of times" and correct the misprint.
Little wonder that precision genetic engineering has taken a while to arrive. In truth, it has been moving steadily toward greater precision for 10,000 years. Early farmers in what's now Turkey introduced a mutation to wheat plants in the "Q gene" on chromosome 5A, which made the seed-head less brittle and the seed husks easier to harvest efficiently.
They did so unknowingly, of course, by selecting from among random mutations.
Fifty years ago, scientists used a nuclear reactor to fire gamma rays at barley seeds, scrambling some of their genes. The result was "Golden Promise," a high-yielding, low-sodium barley variety popular with (ironically) organic farmers and brewers. Again, the gene editing was random, the selection afterward nonrandom.
Twenty years ago, scientists inserted specific sequences for four enzymes into rice plants so that they would synthesize vitamin A and relieve a deadly vitamin deficiency—the result being "golden rice." This time the researchers knew exactly what letters they were putting in but had no idea where they would end up.
In recent years, it has become possible to insert a DNA sequence into a specific location on a chromosome using "zinc finger proteins," which recognize target sequences. But these will work only for certain sequences, and with low efficiency. More recently, a process known by the acronym Talens has proved more adaptable.
This week, Recombinetics of St. Paul, Minn., patented gene-editing technologies that employ Talens for use in livestock improvement. As a first application in agriculture, Recombinetics has used Talens to introduce into Holstein dairy cattle the key mutation (found naturally in Red Angus beef cattle) that keeps horns from growing. The plan is to avoid having to physically dehorn dairy calves, a stressful and expensive procedure.
Scott Fahrenkrug, chief executive of Recombinetics, points out that you could crossbreed Holstein and Angus to achieve the same result, but it would dilute the milk-producing traits in the Holstein. The firm aims to produce pigs and cattle that are more resistant to disease and to use the technology to correct fertility-compromising mutations in cattle that have emerged in selective-breeding programs.
The latest technique, from a team led by Feng Zhang of MIT, promises to be even cheaper than Talens, but it is still in the early stages of development. It hijacks a recently discovered genetic trick that bacteria use to fight off viruses, known by the acronym Crispr. One of the Crispr enzymes in particular, Cas9, the scientists report, can be used for "precise cleavage"—accurate DNA cutting—in human and mouse cells. Moreover, both Talens and Crispr can be aimed at several sites simultaneously—greatly accelerating the process of gene editing.
Precise, multiple editing of DNA has arrived. "I'm expecting a revolution in genetics," says Dr. Fahrenkrug.
