Feb 13, 2014 6:23 PM GMT
Over the last decade, as DNA-sequencing technology has grown ever faster and cheaper, our understanding of the human genome has increased accordingly. Yet scientists have until recently remained largely ham-fisted when they’ve tried to directly modify genes in a living cell. Take sickle-cell anemia, for example. A debilitating and often deadly disease, it is caused by a mutation in just one of a patient’s three billion DNA base pairs. Even though this genetic error is simple and well studied, researchers are helpless to correct it and halt its devastating effects.
Now there is hope in the form of new genome-engineering tools, particularly one called CRISPR. This technology could allow researchers to perform microsurgery on genes, precisely and easily changing a DNA sequence at exact locations on a chromosome. Along with a technique called TALENs, invented several years ago, and a slightly older predecessor based on molecules called zinc finger nucleases, CRISPR could make gene therapies more broadly applicable, providing remedies for simple genetic disorders like sickle-cell anemia and eventually even leading to cures for more complex diseases involving multiple genes. Most conventional gene therapies crudely place new genetic material at a random location in the cell and can only add a gene. In contrast, CRISPR and the other new tools also give scientists a precise way to delete and edit specific bits of DNA—even by changing a single base pair. This means they can rewrite the human genome at will.
It is likely to be at least several years before such efforts can be developed into human therapeutics, but a growing number of academic researchers have seen some preliminary success with experiments involving sickle-cell anemia, HIV, and cystic fibrosis (see table below). One is Gang Bao, a bioengineering researcher at the Georgia Institute of Technology, who has already used CRISPR to correct the sickle-cell mutation in human cells grown in a dish. Bao and his team started the work in 2008 using zinc finger nucleases. When TALENs came out, his group switched quickly, says Bao, and then it began using CRISPR when that tool became available. While he has ambitions to eventually work on a variety of diseases, Bao says it makes sense to start with sickle-cell anemia. “If we pick a disease to treat using genome editing, we should start with something relatively simple,” he says. “A disease caused by a single mutation, in a single gene, that involves only a single cell type.”