TALENs technology allows site-specific gene mutation and editing in living organisms

October 1, 2012
Ying Wang, left, and Jeffrey Essner, right, are breaking ground in advancing techniques to edit the genes of zebrafish. Credit: Robert Elbert.

(Phys.org)—Iowa State University researchers are helping to advance new techniques that allow scientists to site-specifically mutate and edit the genes of living organisms.

The two researchers, co-authors of a study published this week in the journal Nature, are breaking ground in making custom changes to the genome of live zebrafish by utilizing site-directed known as transcription activator-like effector nucleases (TALENs).

Through the TALENs system, researchers for the first time are able to cut out portions of zebrafish DNA and insert artificial replacements. That allows researchers to deactivate – and possibly activate – targeted genes, opening new possibilities to study genetics during early development as well as .

The innovation could have sweeping applications in agriculture and the study of human disease, said Ying Wang, a postdoctoral research associate in genetics, development and and one of the co-first authors of the study.

"This work has very far-reaching implications on many fronts," Wang said. "It could lead to more effective in crops and production animals, and it has the potential to offer new insights into and human disease."

The zebrafish is a small, freshwater species, usually only a few centimeters in length, that wouldn't look out of place swimming around a pet store aquarium. The ISU researchers keep about 8,000 of them in tanks on campus to conduct their research, and, despite their common appearance, zebrafish possess several traits that make them ideal model organisms for genetic study.

For instance, zebrafish embryos are fertilized outside of the mother's body, where they are easy to collect and study, said Jeffrey Essner, an associate professor of genetics, development and cell biology and a co-author of the paper. The embryos are also transparent and can be studied easily under a microscope, Essner said. Finally, a single zebrafish can spawn up to 400 embryos in a single day, providing plenty of material for studies of gene manipulation.

Essner said zebrafish share roughly 90 percent of their genetic makeup with humans, so studying their development can shed new light on human disease. That's especially true during the early embryonic stages of development, he said.

"Most cancers are caused by sporadic mutations in genes over time," Essner said. "What we're doing here could lead to the ability to manipulate those genes, even in an adult."

The ability to activate zebrafish genes – essentially switching them on and off – could lead to breakthroughs in treatments for cancer and a range of other diseases in humans and animals, he said.

Wang and Essner contributed to a team of 16 credited co-authors on the paper, which was led by Stephen Ekker, a molecular biologist at the Mayo Clinic in Rochester, Minn. The paper, titled "In vivo genome editing using high-efficiency TALEN systems," describes the team's effort to make TALENs technology more efficient and to create precise gene-editing techniques.

The TALENs technology has roots at Iowa State, Wang said. Adam Bogdanove, a former ISU professor of plant pathology and microbiology, laid much of the groundwork for the techniques utilized for the paper along with Dan Voytas, also a former ISU professor; Bing Yang, an assistant professor of genetics, development and cell biology; and Martin Spalding, a professor of genetics, development and cell biology.

Since then, TALENs technology has been used to manipulate the genetics of cells, but Essner said that Ekker's group is the first to use TALENs to edit genes in vivo, meaning in a living organism. The paper is the product of more than a year of collaboration among the 16 co-authors, requiring monthly webinars and close cooperation, he said.

"We're just thrilled to have been part of this collaborative effort," he said. "We can't wait to move forward and continue to perfect these gene editing techniques."

Explore further: Researchers develop editing toolkit for customizing zebrafish genomes

Related Stories

Zebrafish: It's not your parents' lab rat

July 30, 2007

Zebrafish cost about a dollar at the pet store. They grow from eggs to hunting their own food in three days. Adults can lay up to 500 eggs at once… and you have more in common with them than you think.

Recommended for you

Scientists create first stable semisynthetic organism

January 23, 2017

Life's genetic code has only ever contained four natural bases. These bases pair up to form two "base pairs"—the rungs of the DNA ladder—and they have simply been rearranged to create bacteria and butterflies, penguins ...

New steps in the meiosis chromosome dance

January 23, 2017

Where would we be without meiosis and recombination? For a start, none of us sexually reproducing organisms would be here, because that's how sperm and eggs are made. And when meiosis doesn't work properly, it can lead to ...

Research describes missing step in how cells move their cargo

January 23, 2017

Every time a hormone is released from a cell, every time a neurotransmitter leaps across a synapse to relay a message from one neuron to another, the cell must undergo exocytosis. This is the process responsible for transporting ...

Lab charts the anatomy of three molecular channels

January 23, 2017

Using a state-of-the-art imaging technology in which molecules are deep frozen, scientists in Roderick MacKinnon's lab at Rockefeller University have reconstructed in unprecedented detail the three-dimensional architecture ...

Immune defense without collateral damage

January 23, 2017

Researchers from the University of Basel in Switzerland have clarified the role of the enzyme MPO. In fighting infections, this enzyme, which gives pus its greenish color, produces a highly aggressive acid that can kill pathogens ...

Provocative prions may protect yeast cells from stress

January 23, 2017

Prions have a notorious reputation. They cause neurodegenerative disease, namely mad cow/Creutzfeld-Jakob disease. And the way these protein particles propagate—getting other proteins to join the pile—can seem insidious.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.