Gene Edition: A new opportunity for Latin America

Published at: 29 November 2022

It is estimated that this technique can drastically reduce breeding times and produce a radical advantage in the generation of improved animals and plants, due to its lower cost and greater accessibility.

The selection of better genotypes -plants or animals -depends on the existence of genetic diversity.
The natural genetic variability generated throughout evolution as a product of mutations, polyploidization and genetic recombination has been used by genetic breeding programs with the aim of generating materials adapted to agricultural production. However, in some crops this variability was reduced as an inevitable consequence of the selection of individuals with favorable characteristics. Different technologies have enabled the reintroduction of variability from crosses (intra- or inter-specific and intergenic), induction of mutations and, more recently, genetic engineering. These techniques are basic tools in breeding because they contribute to enrich the substrate on which anthropic selection is exercised.
Recently, a new tool based on genetic engineering, called gene edition (GE) emerged. GE has the potential to make modifications in the DNA sequence aimed at specific genes to alter their expression (silence or over-expression), replace alleles (introducing favorable alleles) or introduce transgenes into specific sites of the genome. In the first two cases, the EG does not incorporate foreign sequences of DNA (if done by transient expression of the editing machinery) so that the products developed by EG are indistinguishable from those generated by conventional breeding.
EG constitutes a significant advance in genetic modification technologies with a consequent impact on the increase in variability.
It is estimated that this technique can drastically reduce breeding times and produce a radical advantage in the generation of improved animals and plants, due to its lower cost and greater accessibility. In addition, in agámic reproduction crops such as potatoes, banana, cassava, sugar cane or vine, among others, the use of the EG can substantially modify the scheme of breeding programs, since it would allow incremental improvements on established and adapted genotypes (elite).

Conceptual framework of the gene edition

The gene edition allows the mutation of specific regions of the genome through a specific DNA nuclease - organized by a protein guide (ZFN, talen) or RNA (CRISPR) - which causes cuts in a double chain.
These cuts are repaired by the cellular machinery itself with the possibility of introducing errors (deletions or inserts)
that alter promoting regions or the reading frame, causing the virtual "off" of the gene in question.
Alternatively, the elimination of the entire coding sequence of a gene is also feasible.
Also, by union of homologous ends it is possible. Similarly, this technique allows you to create specific insertion sites for one or more transgenes.

Regulation of developments derived from the gene edition

The possibility of generating modifications in the DNA sequence in the absence of foreign genetic sequences has determined, in some countries of the region, that the improved agencies by EG do not present special regulatory requirements such as OGMS for commercialization, and, and, and, and, and,
In turn, they are subject to the same regulations as those obtained by conventional breeding techniques.
In particular, it is expected that the disputed scenario of the intellectual property of this technique will not be restrictive to innovation by small and medium enterprises and public R&D organizations (universities, INIAS), promoting the development of grassroots companies Biotechnological supported by the knowledge of genomes and the functionality and allelic diversity of genes with impact on the phenotype.

Biotechnology opportunities in plants via gene edition

At present, the global community of researchers who use CRISPR has more than 40,000 members in 20,000 institutions, who have documented their research in more than 20,000 studies reviewed and published by pairs in indexed magazines (Kuiken & Kuzma, 2021).
The EG has been carried out experimentally in a series of important agricultural crops, such as rice,
corn, soy, potato, barley, sorghum and wheat, as well as forest species such as poplar. This has allowed the modification of various agricultural interest traits such as
herbicide resistance, tolerance to diseases and drought and the modification of chemical and/or nutritional composition
of harvest products. In this last aspect, it is interesting to note that there is a tendency to improve phenotypic features for the benefit of the consumer (Nutritional quality, chemical composition), the processing of the raw material (industrial quality), the sustainability of the systems through greater efficiency in the use of resources and a lower use of agrochemicals.
Some examples of developments from EG in the region aimed at the benefit of the consumer and the improvement of nutritional quality involve the control of oxidative browning in potato tubers, apples, cane and vines extracts through the loss of polyphenoloxidase function.

Other projects point to the decrease in anti-nutritional compounds in soybeans and potato tubers; In the latter, also increasing quality maintenance during storage, a factor with an impact on the industry.
From the point of view of environmental sustainability, in the different countries of the region, water use and drought resistance in soybeans, potato, rice, beans, sorghum, corn and pastures; as well as in the increase in the genetic resistance of soybeans, wheat, rice and forage species against fungal diseases, developments that will positively impact a decrease in fungicides.

Challenges in Animal Biotechnology

EG in animals has great potential to favor food production. You can promote desirable alleles, genes or mutations that are in low frequency in a population through gene edition, increasing the proportion of individuals who show the desired feature, making them available for animal breeding. In addition, the genomic characteristics associated with unique favotypes to other races or subespecies can be incorporated with precision in the genome of the species of interest to promote a better production and quality of food, as well as favoring animal well -being.
Through the addition of simple but precise mutations, the EG offers the opportunity to generate animals that produce milk of better nutritional quality -like that with the highest proportion of conjugated linoleic acid and proteins beneficial to human health -, or, with inhibition in the secretion of allergenic proteins such as β-lactoglobulin. On the other hand, you can also favor the introgress of favorable genes or alleles. Recently, the dominant polled allele - responsible for the absence of horns, common in British races such as angus - introduced via EG in cells from a bovine with
horns and, after the production of clones of embryos, homozygous animals were generated for the absence of horns. With the introgress of this allele, the Chemical or “to iron” made in the first months of life in calf calves, contributing to the well -being of animals and the rodeo management.
Likewise, the homochigotic character of said gene in edited animals ensures that the parent derived from the semen of them retains the desired character.
Recently, the generation of resistance to the respiratory and reproductive syndrome of pigs (PPRSV) has been reported through the edition of the gene that encodes for a surface receiver of the cells, which is necessary for the virus to trigger the infection. While these developments are still incipient, They open the possibility of identifying "susceptibility" genes to viral and bacterial diseases for the generation of genetically resistant animals, with the consequent impact on the decrease in antimicrobial treatments.
Advances in genomic and phenotypic studies can guide the EG for complex polygenic characteristics, such as those associated with heat tolerance and parasitic resistance such as ticks. Ruminal microorganisms can also be edited to improve digestibility or reduce methane gas production associated with the greenhouse effect. Meanwhile, lost rusticity features with the phenotypic selection could be reintroduced in the genome of improved breeds and thus increase the variability in the population.
Another application of the EG is the generation of animals for model of human health studies or for the production of biopharmacus. As an example, pigs, they show a great physiological and metabolic similarity with humans and their genome could be published to serve as a model for human disease studies, such as cystic fibrosis and heart disease, and for the production of "humanized" organs for use in xenotransplants.

Prospective analysis and opportunities for the region

The gene edition represents an unprecedented opportunity for the development of improved genotypes, both animals and plant that improve the productivity and sustainability of our
productive systems, generating developments of higher nutritional and industrial quality and with value added. This technology constitutes a potential technological revolution, due not only to its particular technical advantages but to the possibility of introducing genetic modifications with high efficiency and unusual speed, since a capacities platform is installed, the characteristics that are desired are properly chosen Improve and dispose of the appropriate elite germplasm. At the same time, as mentioned, several countries in the region have considered that the EG products would be equivalent to those obtained by conventional breeding and they would require the same evaluation of the criteria of novelty, stability and homogeneity, such as any new cultivation to be registered and protected, which would facilitate its arrival to production and market.
As an additional advantage, the possibilities of innovation multiply and enhance depending on the understanding of genomes, genes, their regulation and finally their impact on the phenotype. This raises a scenario where knowledge is the main key for innovative and non -dependent developments of the intellectual property of a gene, as is the case of traditional OGMS.
In this scenario, and considering the overall importance of the region in food production, it is considered that the inias together with other public research institutions, such as universities, have a fundamental role to achieve adequate horizontal collaboration in development and implementation of the EG throughout the region, rescuing the spirit of cooperation between countries and promoting public-private collaboration and the potential creation of biotechnological base companies.
Likewise, it is necessary (re) to create the instances to stimulate technical integration throughout the chain, from those who dominate molecular engineering techniques (EG, in this case) to geneticists and phyto - and zoo - improvers with their leading role in defining the characters and genotypes of greater interest that will be the basis of the variability generation projects to be used in the breeding programs.
Finally, and based on the lessons learned in the past, it is essential to involve consumers and industry as the final recipients of the products derived from the EG, whose acceptance is a basic requirement.
Finally, it should be noted that it would be desirable to develop projects that solve problems of the region or
Of each country. For example, improving post -harvest quality characteristics in fruits or products that must travel to distant markets, develop or optimize pest defense systems and endemic and/or quarantine diseases, among others. Likewise, native or "orphaned" species should be considered, and their potential impact on socio-economic and productive aspects.

The Fontagro Project "Gene Edition for Breeding in Plant and Animal Species", takes this diagnosis and the challenges ahead. It articulates the INIAs from Argentina, Brazil, Colombia, Chile, Ecuador, Paraguay and Uruguay; the universities of Buenos Aires (Argentina) and the Republic (Uruguay); producer organizations such as the Association of Argentine Cooperatives or the Papa Chile and private companies such as Don Mario Semillas; with the financing of FONTAGRO and PROCISUR.
It is proposed, fundamentally, to generate technological abilities that allow the creation of new genetics for both high relevance crops for the region, as well as for animal species whose products are key to future food security. To do this, an inter -institutional platform for research and application of gene edition knowledge will be created.

- González MN, Massa Ga, Andersson M, Turnon H, Olsson N, Fält As, Storani L, Tenth Oneto Ca, Hofvander P, Feingold Se; 2020; Reduced enzymatic browning in potato tubers by specing editing of a polyphenol oxidase gene via ribonucleoprotein complexes Delivery of the crispr/cas9 system. Front Plant Sci. 2020 Jan 9; 10: 1649. DOI: 10.3389/FPLS.2019.01649. PMID: 31998338; PMCID: PMC6962139.
- Kuiken, T.; Kuzma, J.; 2021; Gene edition applied to agriculture: summary of the regional regulatory framework in Latin America; IDB and Center for Genetic Engineering and Society, North Carolina State University;
- WTO - Committee on sanitary and phytosanitary measures. G/SPS/Gen/1658/Rev.4 - International Statement on Agricultural Applications of Precision Biotechnology. (2020).

With the support of
Fondo Coreano de Alianza para el Conocimiento en Tecnología e Innovación (KPK)