From the pig, to the walk, says the popular saying. What the first person who pronounced it perhaps did not imagine is how much the animal hid, beyond what is obvious to the naked eye. Because, although in Spain the pig sector is of key importance in the economy, since -according to figures from the Ministry of Agriculture, Fisheries and Food- it accounts for around 14% of Final Agricultural Production; there is a much more striking fact for the effects of impact on people: pigs share more than 90% of their genes with humans. A recent discovery, if one takes into account that it was in 2012 when the magazine ‘Nature’ published its genome, and that it is not only useful when it comes to understanding the physiology, productive characteristics and history of the species, but also , has important implications for the use of pigs in biomedicine.
Thus, for example, it is known that several of the mutations found in these animals are associated (when they occur in humans) with an increased risk of diseases such as Alzheimer’s, diabetes or, curiously, dyslexia. Another of the lines in which progress is being made is that of xenotransplants (transplants carried out from animals to people), in which genetic similarity is especially important in order to avoid rejection.
At the University of Murcia, the professor of Physiology, Joaquín Gadea, and the group of Reproduction Physiology led by Pilar Coy, have had a line of research focused on swine gene editing for years, related to both the livestock sector and with human medicine.
“Recently, we have made some progress, developing new gene editing methodologies using electroporation and lipofection, and advancing models for xenotransplantation and resistance to swine virus diseases that may have a major impact on human health and the environment in the near future. agri-food sector”, points out the researcher.
Today they already have a viable product catalog that could be marketed, although they are still working on the project.
The team has funding for the validation and scaling of gene editing techniques with applications in the biomedical and livestock fields from the Seneca Foundation-Agencia de Ciencia y Tecnología de la Región de Murcia, within the framework of its aid program for the carrying out projects for the development of scientific and technical research by competitive groups.
According to Gadea, today they already have a viable product catalog that could be marketed, although they continue to work and advance with the project. Specifically, she details, “we have been contacted by those interested in pigs with cardiovascular disease, since it is a problem widely studied in mice, but pigs offer a reality that is closer to humans and that option already exists.”
Groups from all over the world are awaiting the work of Murcian researchers and attentive to knowing the details of their services: costs, deadlines, etc. There is interest in work on neuromuscular diseases, rare diseases and even degenerative diseases of the retina, among others.
From embryos to piglets
“Currently, we have the capacity to develop embryos with different characteristics, although there are more limitations for them to become piglets”, points out the professor. Among others, they have an animal model in which to study calcium signaling, a cellular coordination mechanism, related to numerous physiological processes developed in collaboration with the University of Oxford. Likewise, they already work hand in hand with the Hospital General Universitario Los Arcos del Mar Menor (San Javier), which gives them the opportunity to carry out cooperative work between clinicians and researchers and will allow them to reach new milestones by working in a multidisciplinary way. .
For now, the researchers are focused on two main lines. On the one hand, developing and optimizing work methodologies that make it possible to generate gene-edited animals more efficiently, which consists “in improving the tools we have available so that we can make many products safely, with animal welfare and efficiency. As it is a very complex system with many phases, we can try to improve each one of them”, affirms the professor.
On the other hand, they seek to apply all the methodologies developed for various models, both in the biomedical and agricultural fields. In the latter, specifically, they have focused on resistance to swine virus diseases (SRRP, porcine reproductive respiratory syndrome, swine flu virus and others). The possibility of having animals that do not suffer from viral disease or spread it is a great advance, both for the welfare of the animals and for the producers and people whose food depends on those animals.
In the case of Biomedicine, the UMU group works with models of human diseases. “We work with groups from different places (Oxford, Biodonostia, CNIC, etc.) to develop animals that allow us to advance in the knowledge of diseases and in the development of effective therapies,” says Gadea.
And, in the field of xenotransplants, they have already obtained the first embryos with simultaneous mutations for several KO genes, necessary to avoid rejection. “This field is going to have a breakthrough in the coming years,” he says.
Likewise, they have developed a lipofection technology, through the use of Crispr-Cas, which allows them to modify oocytes and embryos quickly and economically. In the words of Gadea, “it will make it possible to democratize gene editing.”
And he adds: «The efficiency of the method can still be improved, but a new possibility opens up, since up to now not much progress had been achieved. Only in Japan have other researchers been able to use Crispr-Cas in this sense, but eliminating the zona pellucida of the ovules, which made their development unfeasible. On the other hand, we have achieved it without that being necessary.
Another methodological advance achieved by the group from the University of Murcia is related to a technique called electroporation, which consists of placing the oocytes in an electric field and allows momentarily destabilizing the membranes and allowing the Crispr-Cas components to pass through them. the cell to carry out its function of selective editing of the genome at the specific point, where it interests them, and whose use is highly developed for a single gene, but that they have been able to carry, simultaneously, up to five genes, with prominent use in xenotransplantation models.
market launch
Getting to sell a product developed within the university is not easy. In the case of the Reproductive Physiology group, they have been immersed, for three years (pandemic in between), in the creation of a spin-off company, for which they have the support of the entrepreneurship office and the OTRI of the UMU, as well as with the financing of the Ministry of Business, Social Economy and Self-Employed, through the General Directorate of Commerce and Technological Innovation, within the +Spin-Off UMU program. The help is mainly focused on carrying out the business plan and other complex procedures. They have also received help from the Seneca Foundation in the Proof of Concept program.
“This is a complicated technology to patent and, due to its characteristics, associated with animal and human health, as well as its ethical implications, it requires specific and very demanding permits that are not easy to obtain,” concludes Joaquín Gadea.
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