advertisement-vertical Download Proto magazine app
Social Icons
The proteins could offer a better route to gene therapy // Yet researchers face a difficult choice in getting their hands on them // Follow a protocol that takes extensive time and effort // Or shell out thousands to the one company that creates them.

Zinc Fingers: Entry Fee

By Rachael Moeller Gorman // Photographs by Dan Saelinger // Fall 2010
icon-pdfpdf icon-printprint
zinc fingers, cylinder

Dan Saelinger

To understand the growing excitement about zinc finger nucleases—a medical innovation with an odd name and a controversial history—think about how AIDS wrecks the human immune system. In its normal progression, the human immunodeficiency virus, HIV, uses the protein produced by a particular gene to gain entry into immune system T cells. When a sufficient number of T cells are destroyed, often after several years, the immune system can no longer function properly, leaving the body at the mercy of every passing infection.

However, for a fortunate few people who happen to have a mutation in that gene, HIV poses little or no threat, because inactivation of the protein prevents the AIDS virus from entering T cells. If scientists could replicate the effect of that natural mutation, it might confer immunity to HIV. That has long been the hope of gene therapy—that a particular gene could be somehow altered or replaced to produce a desired therapeutic effect. There has never been an effective way to cause a particular mutation in a particular gene, however, and the usual method of dumping corrected versions of human genes into the body has seldom worked as planned.

Now there’s a new approach involving an engineered protein known as a zinc finger nuclease, or ZFN. In studies with the University of Pennsylvania and the University of Southern California, scientists from a California company, Sangamo BioSciences, have “knocked out” the HIV-implicated gene in human T cells and hematopoietic stem cells, thus blocking the AIDS virus’s access to T cells. Sangamo has moved on to a Phase I clinical trial with HIV-positive patients, whose cells were changed with zinc fingers and then transfused back into their blood. The hope is that the patients now have immune cells invulnerable to HIV. In January the University of Pennsylvania researcher in charge of the study reported results from one patient whose body appears to have tolerated the mutated T cells, which were still active 20 weeks after being introduced. If larger trials show similar results, HIV may become easier to treat.

During the past few years, zinc fingers have been popping up everywhere in biomedical research, with applications not only in gene therapy but also in creating knockout rats and manipulating embryonic stem cells. “This technology is transformative,” says Dan Voytas, a researcher at the University of Minnesota. “We are opening the door to a new era in genome modification.”

But there’s a catch. Until recently, the most established way to make zinc fingers was Sangamo’s patented method, and only Sangamo and its close collaborators could use it. Now the company has licensed its technology for research and other applications to Sigma-Aldrich, a large biosciences firm that makes chemicals and biochemical products and kits, and Sigma will create customized zinc finger nucleases for scientists who can afford a price tag of approximately $30,000. (Discounts do exist for academic researchers and those buying multiple nucleases, says Sigma, adding that the price will come down as volume increases, and if a scientist orders a ZFN the company has already made, the cost drops to about $10,000.) Others can turn to the Zinc Finger Consortium, a group of academic researchers that has developed its own way to make the proteins. Though the effectiveness of these proteins hasn’t been compared directly with Sangamo’s, a handful of laboratories have successfully created them, and many more have expressed interest in doing so. The proteins cost much less than Sangamo’s, but while Sangamo’s ZFNs come ready to use, the consortium’s protocol requires a dedicated effort (and significant staff time) of several months to get up and running. All of this raises a question: Business is essential for developing new technologies, but is the business of making zinc fingers actually getting in the way of the science of curing disease?

previous // next
icon-pdfpdf icon-printprint

Zinc Fingers: Business Meets Science

A look at the costs of accessing zinc finger nucleases for research.


1. “Proprietary Science, Open Science and the Role of Patent Disclosure: The Case of Zinc-Finger Proteins,” by Subhashini Chandrasekharan et al., Nature Biotechnology, Feb. 9, 2009. The authors explore the pros and cons of a single company controlling the intellectual property for a potentially game-changing technology.

2. “The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation,” by Aaron Klug, Annual Review of Biochemistry, July 2010. Klug provides a detailed account of how he discovered zinc fingers and notes their potential applications.

3. “Oligomerized Pool Engineering (OPEN): An ‘Open-Source’ Protocol for Making Customized Zinc-Finger Arrays,” by Morgan Maeder et al., Nature Protocols, Sept. 17, 2009. A how-to manual for this weeks-long protocol used to make one’s own set of zinc fingers.

Protomag on Facebook Protomag on Twitter