Gene-editing with engineered nucleases was named 2011 Method of the Year by Nature Methods last month for its contribution to a more accurate, effective, and predictable way to target DNA sequence and repair defect genes. Dr. Adam Bogdanove and Matthew Moscou, a formerl ISU graduate student discovered how TAL effecter, a class of protein produced in plant pathogenic bacteria, is targeted to DNA sequence.

“As a biologist, we want to understand how cells function for fundamental interest, so we can manipulate cell function”, said Adam Bogdanove, professor in Plant Pathology and Microbiology. Gene engineering help to figure out how a cell gets sick, why there is genetic disorder like cancer and provide possible solution to genetic disorder. That is what biologists do to make our life better.

TAL effector is transcript activation-like (TAL) effecter, named by Bing Yang, assistant professor of genetics, development and cell biology. It is a type of protein that pathogens present to a host during infection. The bacteria that produce TAL effecter is a very large group of bacteria that infects many different types of plants, like rice, cabbage, soybeans and so on, according to Bogdanove.

TAL effecters are very important thing for the bacteria to cause disease because wWithout TAL effecters, they can’t grow in the host. The magic of TAL effectors is that it could go out to the plant cell nucleases and find those targeted genes, and turn on those genes directly.

According to Bogdanove, with this method, scientists can make new protein. It is a revolution for the field of DNA targeting. What this protein can do is to find the DNA sequence where there is a problem, cut the DNA sequence and repair it with a sequence of a normal function DNA, like a patch.

The other reason that it is a revolution is that this method dramatically increased the accuracy of gene-editing. Traditionally, if a gene is needed in a DNA sequence, the gene just has to have somewhere to go in. The expression of the gene can be influenced by the DNA at either side of it. The insertion of the gene can cause some trouble.

“It’s a messy process, but with DNA targeting, we can make it double strength to break where exactly we want, and get the gene go in exactly where we want.” said Bogdanove.

There are many genetic disorders that people have. It destroys their ability to make some enzymes which make people die prematurely and makes people very sick because of genetic disorders. A traditional cell therapy approach is to take cells from healthy human donor and inject those cells, but just like doing liver transplant or lung transplant, you have to suppress the patient’s immune system.

“What if you can take the patient’s own cells, take them out of a patient and repair them, and put them back to the patient?” said Bognadove. “That is really exciting. That is why Nature Methods called gene-editing with engineering nucleases method of the year.”

The success of this discovery benefit from many scientists’ hard work. Matthew Moscou, who did the computation work for this discovery mentioned that the biggiest challenge was determining how far we could get with the analysis. After a lot of trial and error, they were able to scan all the gene promoters and pull out target genes.

With the advent of this method, lots of work is currently ongoing with testing the feasibility of TAL effectors in performing exactly. 2010 a group in Minnesota led by Dan Voytas, director of the Center for Genome Engineering at the University of Minnesota, former professor in genetics, development and cell biology at Iowa State, led a project to test this TAL effecter nucleases to build the test and it worked.

According to Bogdanove, a series of papers showing the use of TAL effectors and TAL effectors nucleases can be use in several different mechanisms, different cell types including plants, zebra fish, cancer research, and also human cells. What remains is just to work out the details, and optimize their use and start to employ them for therapies.

Dan Voytas expressed that there are numerous applications of this technology, from creating new crop plants to correcting inherited genetic disorders.

“I truly believe the technology deserves recognition as method of the year.” said Voytas.

Dr. Bogdanove’s lab made the protein kit publicly available immediately they published the paper in 2009. Now, at least 270 labs across the world are trying out TAL effectors. They also built a website with a computational tools to help design TAL effectors. So far there are about 7000 users including 3000 independent users of that website.

To understand TAL effecter protein better, structural biologists use X-rays to see the protein structure and provide 3D model of it. With this model, scientists have a better idea of how TAL effecters interact with DNA. Scientists may use this model to make predictions more precisely.

“It is amazing structure, we never see anything like this before in nature. We never see any protein that wraps up with DNA like this.” said Dr. Bogdanove.

Gene-editing with engineered nuclease helps people to understand how simple and effective of the bacteria in some strategy to inject the host cell to make the plant sick for their own benefits, said Professor Bing Yang. People take advantage of simple sense to make good thing out of it. However, TAL effecter is not the ultimate method to fix all the genetic disorder problems. According to Bogdanove, the science community has a lot to do yet. It is still young, still in early time right now.