A Brazilian startup called Kimera Biotecnologia, based in Ribeirão Preto, Brazil, has produced the first biotech version of equine chorionic gonadotropin (eCG), a hormone widely used to induce and synchronize estrus in cattle and pigs, with the aim of optimizing the results of artificial insemination.
Already tested in both species, the new recombinant eCG (r-eCG) has proven as effective as the conventional version, with the advantages of having between 30% and 50% lower production costs, according to Kimera, and eliminating the controversial use of pregnant mares to produce the hormone.
Since conventional eCG was first used in livestock reproduction more than three decades ago, it has been obtained from the blood of pregnant mares, frequently resulting in ill treatment, abortions, and the premature death of these animals.
"Kimera's hormone is entirely produced in the laboratory without the need for extracting blood from mares or any other animal, and at far lower cost," says Camillo Del Cistia Andrade, a founding partner in Kimera and principal investigator for the research project. Andrade holds a PhD in genetics from the University of São Paulo (USP).
The demand for eCG is rising with the growing use of artificial insemination as a basic tool to accelerate genetic improvement and increase livestock productivity. The success of the procedure depends on knowing when females will ovulate. In addition, being able to inoculate many animals or an entire herd at the same time reduces the cost of insemination and permits synchronization with other stages of production, optimizing the production process as a whole.
Breeders of all sizes now use artificial insemination and increasingly employ reproductive hormones to synchronize estrus. In 2010, the technique known as fixed-time artificial insemination (FTAI) accounted for half the insemination procedures performed in Brazil.
Indeed, FTAI is one of the factors that has enabled Brazil to expand its cattle herd by 40% since eCG was first used some 25 years ago and become the world's leading meat exporter. In addition to estrus synchronization, the hormone can also be used to hasten puberty, induce superovulation in females, and rapidly reverse the period of sexual inactivity that follows separation from their young, increasing fecundity.
Technology transfer
Founded in 2014, Kimera had from the start the support from the São Paulo Research Foundation (FAPESP) Innovative Research in Small Business Program (PIPE). It was incubated at the Supera Innovation & Technology Park in Ribeirão Preto, São Paulo State, with the aim of developing r-eCG and similar products and transferring the technology to other firms.
The production of r-eCG in the lab is possible because Andrade succeeded in cloning the gene responsible for producing eCG and inserting it into cultured cells. These cells produce the hormone, which is then purified. With FAPESP's support, Kimera developed an innovative biotech process and applied for a patent jointly with USP.
During Stage 1 of its PIPE project between September 2014 and May 2015, Kimera produced the hormone on a laboratory scale and performed initial tests using rats. Later, tests were conducted to compare the results of r-eCG application with the use of eCG produced in Nelore cows that had given birth at least once: 127 received eCG and 50 were given r-eCG.
All the cows ovulated and were inseminated, with a pregnancy rate of 50.2% in those given the hormone from mares and 48% for those given r-eCG. The difference was not considered statistically significant. Tests in sows yielded similar results, and the same success rate is foreseen with does (female goats) and mares.
In Stage 2, which began in November 2016 and is still in progress, the aim is to study the best way to ramp up the production of r-eCG.
In parallel, Kimera is contacting pharmaceutical companies that produce the hormone to see if they are interested in acquiring the new technology to produce r-eCG themselves. Currently, Kimera buys equine plasma from producers in Argentina and Uruguay and uses the plasma as a basic input to produce eCG.
"We're looking for a private partner for the final stage required to register the product with the Ministry of Agriculture, which is the construction of a pilot plant with the capacity to meet at least 10% of the domestic demand," Andrade says.
Although a plant designed to produce r-eCG would have certain unique specifications, he adds, it would also have much in common with the pharmaceutical industry's existing infrastructure. "A partnership would shorten the time to market, which is in everyone's interest, as it's an innovative product with significant domestic and international market potential thanks to its low cost and because it meets the global demand for the more ethical and sustainable production of hormones for animal reproduction," Andrade explains.
While completing this research project, his team is already studying the possibility of working on the development of new recombinant hormones and vaccines.
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About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships, and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. For more information: http://www.fapesp.br/en.
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