Chemical & Engineering News - Sangamo Mention

CRISPR’s breakthrough problem

If the CRISPR gene editing system is to live up to its disease-curing potential, researchers must devise a plan to deliver it into the body

http://cen.acs.org/articles/95/i7/CRISPRs-breakthrough-problem.html

(note aslo includes discussion of LNP delivery)

snip

Sangamo is using an older gene-editing tool called zinc finger nucleases, a complex protein structure designed to bind and cleave a specific region of DNA. And doctors at the Great Ormond Street Hospital in London recently reported using a similar gene-editing technique called TALENs, which also recognizes and cuts precise DNA sequences, to engineer immune cells for a therapy that may have cured two infants of leukemia.

Both technologies have been around for longer than CRISPR has, with zinc-finger-based editing being in the works for more than two decades. They also both suffer from a limitation that has inhibited their widespread adoption: Each is a cumbersome protein complex that needs to be individually engineered for every new DNA target.

CRISPR, meanwhile, is easily adaptable. The Cas9 cutting protein remains the same for all applications, and to make a new edit, researchers need only to switch out the guide RNA. If the DNA sequence that needs editing is known, securing the complementary guide RNA is as easy as clicking “Order” from a supplier.

“When CRISPR came along, everyone knew what to do with it,” Intellia’s Barnes says. “People had been going around in a go-kart and you gave them a Ferrari, so away they go.”

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CRISPR isn’t the first gene-editing technology promising to cure thousands of diseases. In fact, multiple studies of treatments developed using older technologies are now under way. Drug delivery guru Daniel Anderson of Massachusetts Institute of Technology points out that one of the most advanced programs is Sangamo Biosciences’ ongoing clinical trial to remove T cells from patients, edit their DNA to make them resistant to HIV, and reinject the modified cells. “So presumably, there are some genome-edited people walking around in California that they helped create,” Anderson says.

Although researchers are excited about the potential to use CRISPR to create therapies from people’s own blood, immune, and stem cells, thousands more genetic conditions affect everything else. For those disorders, CRISPR needs to be delivered like more traditional medicines so it can work its wonders editing DNA inside the body. But the challenge of shuttling CRISPR directly to the diseased tissue, or “in vivo” gene editing, is so daunting it could stall CRISPR’s otherwise rapid advancement