08.08.2016

Argentine scientists removed the Mad Cow gene

Research funded by the National Agency for Scientific and Technological Promotion embryos developed on FAUBA and were published in the journal Theriogenology.

Argentine scientists removed the Mad Cow gene

The CRISPR-Cas9 technology allows you to edit the genome of any species (from plants to animals) directly cutting the gene

Facultad de Agronomía de la UBA (FAUBA -The Faculty of Agronomy of the UBA) through Animal Biotechnology Laboratory, managed to eliminate the mad cow gene in embryos from studies developed in collaboration with scientists from Germany and the United States. The achievement represents a breakthrough in fighting a dreaded disease that affects cattle and can be transmitted to humans. But it also allowed the work to fine-tune our country in a new technique of genetic edition, called CRISPR-Cas9 (genetic scissors), which could generate new knowledge in the areas of human medicine and animal production.

The studies were funded by the National Agency for Scientific and Technological Promotion through a PICT-2013 for a total amount of $ 424,038.

The research was published in the July issue of the magazine Theriogenology  and its main author was Romina Bevacqua. The studies were funded by the National Agency for Scientific and Technological Promotion, Ministry of Science and Technology of the Nation, through a PICT-2013 for an amount of $ 424,038 subsidized. In the project "Open Issues transposons for gene and CRISPR edition of sheep and cattle. " Members of Laboratory Animal Biotechnology FAUBA  also attended: Rafael Fernandez Martin, Virginia Savy, Natalia Canel and its director, Daniel Salamone. Also participated in this project: Taboga Oscar and Maria Ines Gismondi, INTA Castelar, and Sergio Ferrari, the Maimonides University. Part of the work was done in collaboration with Heiner Niemann, researcher at the Institute of Farm Animal Genetics (FLI, for its acronym in German), Germany, and the company Recombinetics, Minnesota, United States. In both countries, Bevacqua held many post-doctoral stays.

"We applied this new strategy of molecular scissors to make three types of changes in the genome. On the one hand, we introduced very small changes (mutations) as those that occur naturally, but in a targeted manner to certain genes of interest, which in our case it was the mad cow disease. For this reason, some researchers in the area started talking about accelerated evolution," informed Bevacqua at the United States, popular science site FAUBA, Over the Earth. She continues carrying out her studies at the Rockefeller University.

"Moreover, we prove that it is possible to apply this technology to insert a gene of interest precisely in the gene for mad cow and finally we showed that we can cut out in more than one place of the gene to remove a large fragment thereof or remove it completely," she added.

Mad cow disease, or bovine spongiform encephalopathy, is caused by prions, infectious particles formed by a protein capable of producing degenerative neurological diseases. "By removing this gene, the cow can not be affected by this disease," said Salamone, and clarified that the investigation did not point to generate an animal, but to evaluate the use of tools of genetic editing in order to remove genes of an embryo and replace others of interest. He also clarified that Argentina is a country free of the mad cow disease, but Europe, the United States and other countries have suffered major problems.

The researchers stressed that they managed to eliminate in a laboratory susceptibility to certain diseases and generated new scientific knowledge that benefit both animals and humans, who may also acquire the disease. Salamone and his team believe they are advancing on a new generation of animals produced by these treatments. However, for live specimens resistant to diseases and to turn them into marketable products, further research and investments, plus some changes to the current regulation are required.

Genetic edition

Up to date, the available tools of genetic edition were developed about 12 years ago in the United States and were very costly and inefficient, although they have improved in recent years. "In all animals that we have developed in these decades in our country, the genes we added so far were located anywhere in the genome, somehow random. Whereupon, sometimes do not work well, "said teacher from FAUBA.

Genetic edition opens a field of auspicious research: "For our research we use a new technology that emerged five years ago, very economical and efficient, called CRISPR-Cas9. Unlike previous costly techniques, trying to overwrite the gene, this tool allows you to edit the genome of any species (from plants to animals) directly cutting the gene, "he noted.

He added: "The appeal of our work is not that we only cut, as was done in most of the researches that exist so far, but we did a cut and paste: cut and paste a new gene. So far, it was only a green indicator, but in the future it could be replaced by others that will generate greater benefits ". This means that now the gene is positioned in the exact place chosen by the scientist, which ensures greater efficiency. "We hit the mark," Salamone said.

"In the peculiar case of mad cow, until we changed one amino acid (protein component that generates the disease) for that animal to have resistance. We therefore believe that these subtle changes will allow us in the future to repair genetic diseases or grant resistance ".

Bevacqua extended information: "Up to date, genetic modifications introduced into embryos to generate modified animals in all processes requiring extremely expensive and complex, such as cloning cells. The CRISPR-Cas9 technology also proved to be an efficient injection directly into eggs, which by natural means, such as artificial insemination may occur. So we can obtain a level of intervention in the laboratory to be much smaller. "

"If we add the fact that the system can be introduced as ribonucleic acid - RNA (which is not located on the genome where the objective is only mutating a specific gene), really only a specific change is introduced, as might occur naturally but directed "he said. "46% of the embryos analysed were specifically modified, demonstrating the great potential of this technique. Even when the aim is to insert a gene it would no longer be necessary to co-introduce other genes in order to select, as it was until recently, "he explained, although he considered that some technical issues still need to be improved.


Source:
Facultad de Agronomía de la UBA (Faculty of Agronomy of the UBA). 

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