Cheap And Easy Gene Therapy

A precise and elegant technique for cutting and pasting DNA to insert genes into human cells would radically transform medicine, making routine what now are expensive, complicated and rare procedures for replacing defective genes in order to fix genetic diseases was discovered last year by Jennifer Doudna and Martin Jinek of the Howard Hughes Medical Institute and University of California, Berkeley (and the LBL, too), and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine-Sweden. In the team’s June 28, 2012, Science paper the researchers described a new method of precisely targeting and cutting DNA in bacteria.

This paper caused a little stir, and other scientists began to use the method; two new papers published last week in the journal Science Express demonstrate that the technique also works in human cells. A paper by Doudna and her team reporting similarly successful results in human cells has been accepted for publication by the new open-access journal eLife (don’t be like that.  Times change, man.  Journals are for getting the information out, and e-journals are faster.  So there).

People are already comparing the technique to PCR, the DNA-replicating technique which scored a Nobel for Cary Mullis, in terms of impact on the genetics field.

"I think this is going to be a real hit," said George Church, Professor of Genetics at Harvard Medical School and principal author of one of the Science Express papers. "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."

How does it work? The new technique uses a single protein that requires only a short RNA molecule to program it for site-specific DNA recognition, an enzyme called Cas9, and the replacement DNA.  The nice part is that these molecules are all smaller than the kind of stuff you would have to sneak into a cell to achieve the cut-and-paste effect using the current techniques. "It (the Cas9-RNA complex) is easier to make than TALEN proteins, and it’s smaller," The complex also has lower toxicity in mammalian cells than other techniques, he added. "It’s too early to declare total victory" over TALENs and zinc-fingers (the two competing techniques—bulky and complex—don’t ask), Church said, "but it looks promising."

"The beauty of this compared to any of the other systems that have come along over the past few decades for doing genome engineering is that it uses a single enzyme," Doudna said. "The enzyme doesn’t have to change for every site that you want to target – you simply have to reprogram it with a different RNA transcript, which is easy to design and implement."

The delicious and not at all surprising part of this exciting new technique is that it’s the result of some rather more pure science; Doudna was looking at the unique immune system of a bacteria that cuts the DNA of attacking viruses, incorporates it into its own DNA and uses it to make RNA to intercept the viral DNA, rendering it useless.  Nature is stranger than we imagine, and stranger than we can imagine.

 

Homework:

RNA-programmed genome editing in human cells (accepted for publication in eLife) RNA-Guided Human Genome Engineering via Cas9 (Church article, Jan. 3 Science Express)

Multiplex Genome Engineering Using CRISPR/Cas Systems (Wang article, Jan. 3 Science Express)