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DNA editor named runner-up breakthrough of 2012

TAL effector bound to DNA
Graphic by Jon Bogdanove
A TAL effector bound to DNA. TAL effectors are DNA-targeting proteins that plant pathogenic bacteria use to alter gene expression in their hosts.

A discovery that allows life scientists to precisely edit genomes for everything from crop and livestock improvement to human gene and cell therapy was named runner-up for Science magazine's 2012 Breakthrough of the Year.

The work by Adam Bogdanove, Cornell professor of plant pathology and plant-microbe biology, joined eight other runners-up to Breakthrough of the Year -- the discovery of the Higgs boson -- in the magazine's Dec. 21 issue.

Bogdanove's breakthrough, which came in 2009 while he worked as a plant pathologist at Iowa State University, allows researchers to target and cut DNA in a living cell. Bogdanove identified a DNA targeting mechanism in proteins called TAL effectors that are used by plant pathogenic bacteria to alter gene expression in their hosts.

In 2010 he and collaborators at the University of Minnesota showed that these proteins could be used to carry an enzyme that cuts DNA, called a nuclease, that target specific DNA sequences in an organism's genome. The combination of TAL effector and nuclease is called a TALEN.

"The ability to cut DNA in living cells with TALENs allows researchers to modify DNA with higher efficiency than was previously possible," Bogdanove said. While another technology called zinc finger nucleases can also target specific genes, those nucleases are hard to make, and one company owns most of the patents. TALENs can be easily and cheaply constructed and are widely available.

TALENs give researchers the power not only to target and knock out specific gene sequences, but also to replace them with new DNA. The technology opens the door for medical applications such as gene therapy.

Depending on the nature of, say, a genetic defect, researchers may soon be able to extract a patient's cells, place them in a petri dish, remove the genetic mutation, replace that sequence with healthy code, and reintroduce the patient's own cells, now fixed, Bogdanove said.

Similarly, plant breeders may use TALENs to sidestep traditional breeding of crops by inserting new, site-specific genetic information, he added.

Bogdanove is working to further understand the basic biology of plant bacteria interactions with TAL effectors. "In that context, we expect to learn fundamental things of how these proteins interact with DNA that further inform technology development," he said.

 

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