Kheiron Biotech, an Argentina-based biotechnology company, claims to have created the first genetically-modified equine embryo.
Founded in 2011 in part to meet demand for elite polo horses, Kheiron primarily works in equine cloning but also with cattle breeding and regenerative medicine using stem cells. They’ve produced roughly 200 cloned horses since 2013 and work with customers worldwide. But the future is “precision breeding,” says Dr. Gabriel Vichera, laboratory director and biotechnology and animal reproduction specialist
We caught up with Dr. Vichera, via email, to learn more.
Kheiron recently created one of the first genetically modified equine embryos. What do you hope to accomplish via genetic modification?
Dr. Vichera: Yes, we’ve generated the first genetically modified equine embryos. We chose the edition of the myostatin gene because of its role regulating muscle development in [sport] horses; this gene plays a crucial role as it controls muscle composition and growth. So, when this gene is downregulated, horses have more muscle mass, [a] different proportion of muscle fibers and run faster in short distances. It’s important to note that this is a natural genetic characteristic in some individuals.
In our work, we aimed to generate edited horse embryos by knocking out the myostatin gene, but with this technique available other editions could be achieved, including the correction of genetic defects that cause equine diseases.
Our long-term goal is to identify natural advantageous allele sequences present in the genome of some individuals and incorporate them in others to endow them with the desired characteristics. This breeding system is called “precision breeding.”
To clarify, are “precision bred” horses clones?
Dr. Vichera: Not yet. There [aren’t] precision bred horses.
What advantages will “precision bred” horses have over their non-precision bred counterparts?
Dr. Vichera: The most important concept in precision bred horses is that you maintain all the desired characteristics of the individual and only few specific characteristics are changed. You could have a winner horse and make it resistant to a disease, for example.
In natural breeding, when two individuals are crossed, the offspring do not acquire the desired characteristics from both parents, some are gained and some others are lost.
What are the implications of being able to create and breed genetically modified equines?
Dr. Vichera: By now, we are at an initial experimental step of the technology. However, we consider that horses obtained by precision breeding will have advantages over other individuals. One of the objectives is to find sportive genetic characteristics of excellence, considering those that already exist in nature in individuals of the same species.
We think this technology will give an advantage to those breeders who adopt it over those who do not. That’s why there’ll be many sport horse breeders interested in it. It’s important to note that we are focused on determining natural advantageous genetic characteristics in horses to copy them in other individuals, not to generate a transgenic or genetically modified organism.
On the other hand, the generation of animals by precision breeding will reduce wastage in [the] horse industry because less animals have to be generated to obtain elite phenotypes. In addition, natural and economical resources needed for breeding will also be reduced.
That’s interesting. How much “wastage” is currently produced and how will precision breeding reduce it?
Dr. Vichera: With the conventional breeding systems that are used today, hundreds of births a year are needed to obtain elite sport horses that, for example, will play a triple crown polo championship. These hundreds of births that each breeder must generate annually have a very high associated cost. Cloning is reducing the number of births required to obtain this type of differential horse and precision breeding will reduce them even more.
Let’s go back to the science. So, the myostatin gene correlates to muscle mass and, when edited, can enable horses to run faster over shorter distances. How has this impacted the abilities of polo horses and how could it potentially impact other disciplines?
Dr. Vichera: In polo, it depends on the strategy of the player. More faster and explosive horses per chukker could make the differences at the polo match. In endurance [competitions] more resistant horses would be more suitable instead of faster horses.
You stated, “it is important to note that we are focused on determining natural advantageous genetic in horses to copy them in other individuals, not to generate a transgenic or genetically modified organism.” What differentiates natural advantageous characteristics brought out via precision breeding from a genetically modified animal?
Dr. Vichera: In transgenic animals, DNA from one species is incorporated in other species. In genetically modified animals, one gene could be silenced or activated artificially with DNA sequences that were designed by the [scientist] and are not present in any species.
In precision breeding, the [genome] of one individual is copied to another individual of the same species, one allele changed in for other existing alleles, conserving all other characteristics.
Wouldn’t editing genes, in any form, be considered a type of genetic modification?
Dr. Vichera: According to Argentine regulations, which are based on international regulations such as the Cartagena Protocol on Biotechnology Safety, a genetically modified animal implies a new combination of DNA. In precision breeding no exogenous [external] DNA sequences are incorporated and the genetic modification could be obtained naturally. For this reason, according to Argentine regulations, animals generated by precision breeding through gene editing would not be considered as genetically modified animals.
You mentioned this technology could give an advantage to breeders. What impact will it have on those breeders who don’t adopt it?
Dr. Vichera: It’ll continue to take a long time to acquire genetic progress in their animals and it’ll be much more [expensive] to achieve elite animals.
What are the downsides to cloning and/or precision breeding? For example, if someone interested in precision breeding selected for one trait, could that be to the detriment of a different trait?
Dr. Vichera: This technology is very new and there’s much to learn. Not all the traits are directly related to one gene, so a lot of research is necessary to ensure the modification, both genotypically and phenotypically.
What is the estimated cost of precision breeding?
Dr. Vichera: It is difficult to calculate right now because we are at a very initial stage of the technology. It is probable that the technology is likely to advance and costs to drop significantly the next years. To have an idea, in 2012 a cloned horse cost 50% more than in 2020.
While athleticism is definitely an important characteristic in elite sport horses in any discipline, many top equestrians argue a horse’s “heart” or will to perform is equally important, if not more important. What dispositions or personality traits have been noted in cloned or precision-bred horses and have any reached the same accomplishments as the horse they were cloned from?
Dr. Vichera: This point is very interesting. Only around 20 cloned horses are playing polo, because of their age, it’s necessary the horses have five to seven years to play and the technology is very new. Breeders are surprised because the clone performs like the original. They learn the same or faster and they sometimes are even better.
This is the case [with] Cuartetera, a horse with several clones—some of the clones won in 2018 and 2019. It seems that the personality is conserved in cloned horses.
How significant do you think cloning will be in the future? Could we someday see a full polo team of cloned horses, for example?
Dr. Vichera: Although nowadays we can see teams with five or six copies of the same individual in the same game, we’re convinced that this is not the main advantage of cloning. The most important advantage is to multiply mothers that generate good players, which allows the possibility of generating new combinations with a greater number of stallions.
In addition, cloning allows the return of the reproductive capacity of males that today are elite but that were castrated in their youth.
Cloning also allows the generation of a greater number of offspring of genetic mares that are players and are in competition during their reproductive period.
Another great advantage is that the genetics of dead animals can return to life. By this way, individuals that were genetically important in other times can be crossed with current animals, a process that would otherwise be impossible.