IU research shows limitations to gene editing system


Michael Wade, distinguished professor of biology, recently published a study that revealed the limitations of the gene-editing system, CRISPR. Natural gene Variations in Wild Populations could prevent the system from working as well as researchers previously thought.

When a revolutionary gene editing system called CRISPR was revealed in 2013, researchers couldn’t help imagining the incredible possibilities it could bring — wiping out diseases before they could spread or creating crops that could breed better than ever before.

The gene editing system allows scientists to target specific genes, making it easy to take out different parts of the genome and replace them with whatever CRISPR was designed to create.

One immediate idea for many scientists was using CRISPR to stop the spread of malaria, a disease that affects three billion people globally. Theoretically, scientists could take a mosquito’s DNA and change the gene that allows the insect to carry that disease.

By releasing lab-edited mosquitos into the wild and breeding them with mosquitos already living in nature, they could create a new generation of mosquitos without the ability to host malaria.

The actual execution of this idea was far off and required more research, but it was still in the realm of possibility. But new research from IU biologists show that it may be even further off.

Michael Wade, distinguished professor of biology at IU, published a study May 19 in the journal of Science Advances. The paper outlines a genetic and mathematical analysis that shows naturally occurring variations in genes found in the wild would essentially stop CRISPR in its tracks.

The study focused four varieties of flour beetles. The beetles came from four parts of the world — India, Spain, Peru and Indiana. The team designed CRISPR mechanisms to see how they would react with naturally-occuring gene variations found in the beetles.

The results showed that in all four species and in every DNA segment, there were genetic variations that would prevent CRISPR from spreading and controlling the population after a certain number of generations.

This means that to control a population, scientists would have to create different mechanisms for every type of genetic variation. It’s a costly endeavor that would take time, energy and money to implement.

And that’s if it works.

Variations can be both genetic and behavioral. For instance, mosquitos tend to inbreed, meaning they don’t mate with insects outside of their group.

“If the naturally occurring population is predisposed to mate with its own kind instead of some kind you release from the laboratory, then that subsection of the population will be immune to CRISPR,” Wade said.

The results of the study also show that an unintentional spread of modified genes across the globe is unlikely. Natural variations in genes seen in the flour beetles and mosquitos would place a natural barrier to this possibility.

“One of the messages of our paper is before you engineer a CRISPR construct with the goal of releasing it into nature, you have to study your target population,” Wade said.

Every insect has subsections of their population with different gene variations. These will all react with CRISPR in different ways, making a universal mechanism to control something like malaria impossible for the foreseeable future.

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