Technique to snip DNA could alter gene therapy

The technique was discovered by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden.

“The ability to modify specific elements of an organism’s genes has been essential to advance our understanding of biology, including human health,” said Doudna. “However, the techniques for making these modifications in animals and humans have been a huge bottleneck in both research and the development of human therapeutics.

“This is going to remove a major bottleneck in the field, because it means that essentially anybody can use this kind of genome editing or reprogramming to introduce genetic changes into mammalian or, quite likely, other eukaryotic systems.”

“I think this is going to be a real hit,” said George Church, professor of genetics at Harvard Medical School. “There are going to be a lot of people practicing this method because it is easier and about 100 times more compact than other techniques.”

“Based on the feedback we’ve received, it’s possible that this technique will completely revolutionise genome engineering in animals and plants,” said Doudna. “It’s easy to programme and could potentially be as powerful as the Polymerase Chain Reaction (PCR).”

The latter technique made it easy to generate millions of copies of small pieces of DNA and permanently altered biological research and medical genetics.

Cruise missiles

Two developments - zinc-finger nucleases and TALEN (Transcription Activator-Like Effector Nucleases) proteins - have gotten a lot of attention recently.

Researchers can use these methods to make two precise cuts to remove a piece of DNA and, if an alternative piece of DNA is supplied, the cell will plug it into the cut instead.

In this way, doctors can excise a defective or mutated gene and replace it with a normal copy. Sangamo Biosciences, a clinical stage biospharmaceutical company, has already shown that replacing one specific gene in a person infected with HIV can make him or her resistant to AIDS.

Both the zinc finger and TALEN techniques require synthesising a large new gene encoding a specific protein for each new site in the DNA that is to be changed. By contrast, the new technique uses a single protein that requires only a short RNA molecule to program it for site-specific DNA recognition, Doudna said.

Church compared the new technique, which involves an enzyme called Cas9, with the TALEN method for inserting a gene into a mammalian cell and found it five times more efficient.