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“All domestic animals are thriving, and a bumper harvest for all crops” describes an ideal agriculture that the Chinese farmers have dreamed for thousands of years. With the recent advent of genome editing technologies centered on sequence-specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered, regularly interspaced short palindromic repeat-associated endonucleases (CRISPR/Cas), we are fortunate to see t [Detail] ...
The recent development of genome editing technologies has given researchers unprecedented power to alter DNA sequences at chosen genomic loci, thereby generating various genetically edited animal models. This mini-review briefly summarizes the development of major genome editing tools, focusing on the application of these tools to generate animal models in multiple species.
In recent years there has been a veritable explosion in the use of genome editors to create site-specific changes, both in vitro and in vivo, to the genomes of a multitude of species for both basic research and biotechnology. Livestock, which form a vital component of most societies, are no exception. While selective breeding has been hugely successful at enhancing some production traits, the rate of progress is often slow and is limited to variants that exist within the breeding population. Genome editing provides the potential to move traits between breeds, in a single generation, with no impact on existing productivity or to develop de novo phenotypes that tackle intractable issues such as disease. As such, genome editors provide huge potential for ongoing livestock development programs in light of increased demand and disease challenge. This review will highlight some of the more notable agricultural applications of this technology in livestock.
Genetic modification techniques, in particular novel gene editing technologies, hold the yet unfulfilled promise of altering genetic traits in farm animals more efficiently than by crossbreeding, allowing for a more rapid development of new cattle breeds with distinct traits. Gene editing technologies allow for the directed alteration of specific traits and thereby have the potential to enhance, for instance, disease resilience, production yield and the production of desired substances in milk. The potential implications of these technological advancements, which are often combined with animal cloning methods, are discussed both for animal health and for consumer safety, also with consideration of available methods for the detection and identification of the related products in the food supply chain. Finally, an overview is provided of current regulatory approaches in the European Union (EU) and major countries exporting beef to the EU, for products from animals bred through established practices as well as modern biotechnologies.
Selecting beneficial DNA variants is the main goal of animal breeding. However, this process is inherently inefficient because each animal only carries a fraction of all desirable variants. Genome editing technology with its ability to directly introduce beneficial sequence variants offers new opportunities to modernize animal breeding by overcoming this biological limitation and accelerating genetic gains. To realize rapid genetic gain, precise edits need to be introduced into genomically-selected embryos, which minimizes the genetic lag. However, embryo-mediated precision editing by homology-directed repair (HDR) mechanisms is currently an inefficient process that often produces mosaic embryos and greatly limits the numbers of available edited embryos. This review provides a summary of genome editing in bovine embryos and proposes an embryo-mediated accelerated breeding scheme that overcomes the present efficiency limitations of HDR editing in bovine embryos. It integrates embryo-based genomic selection with precise multi-editing and uses embryonic cloning with elite edited blastomeres or embryonic pluripotent stem cells to resolve mosaicism, enable multiplex editing and multiply rare elite genotypes. Such a breeding strategy would enable a more targeted, accelerated approach for livestock improvement that allows stacking of beneficial variants, even including novel traits from outside the breeding population, in the most recent elite genetic background, essentially within a single generation.
Pigs are one of the most important domesticated animals and have great value in agriculture and biomedicine. Single nucleotide polymorphisms (SNPs) are a dominant type of genetic variation among individual pigs and contribute to the formation of traits. Precision single base substitution provides a strategy for accurate genetic improvement in pig production with the characterization of functional SNPs and genetic variants in pigs. Base editing has recently been developed as the latest gene-editing tool that can directly make changes in single nucleotides without introducing double-stranded DNA breaks (DSBs), providing a promising solution for precise genetic modification in large animals. This review summarizes gene-editing developments and highlights recent genetic dissection related to SNPs in major economic traits which may have the potential to be modified using SNP-editing applications. In addition, limitations and future directions of base editing in pig breeding are discussed.
Transgenic ruminants are a valuable resource for both animal breeding and biomedical research. The development of transgenic breeding is proceeding slowly, because it suffers from low efficiency of gene transfer and possible safety problems from uncontrolled random integration. However, new breeding methods combined with genome editing and somatic cell nuclear transfer or microinjection can offer an economic and efficient way to produce gene-edited ruminants, which can serve as bioreactors or have improved disease resistance, animal welfare and product quality. Recent advances in precise genome editing technologies, especially clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 nucleases, are enabling the systematic development of gene-edited ruminant production. This review covers the development of gene-edited ruminants, the particulars of site-specific engineered nucleases and the state of the art and new insights into practical applications and social acceptance of genome editing technology in ruminants. It is concluded that the production of gene-edited ruminants is feasible and through improvements in genome editing technology it is possible to help feed the world.
Recent breakthroughs in CRISPR technology allow specific genome manipulation of almost all crops and have initiated a revolution in precision crop breeding. Rationally-based regulation and widespread public acceptance are needed to propel genome-edited crops from laboratory to market and to translate this innovative technology into agricultural productivity.
Precision genetics and breeding have the potential to meet the agricultural needs and goals of the world in the 21st century. These needs include increasing the efficiency of production of animals and improving their products with minimal impact on the environment. The USA is the major innovator in genomic science and the acknowledged leader in formulating policies to regulate genetic applications in medicine and agriculture. However, governments worldwide have been exceedingly reluctant to support the introduction of genetically modified (GM) animals into agriculture. Regulatory policies have stagnated due to legal guidelines that could not anticipate the needs and solutions that are evident today. This must change if we are to maintain planetary integrity. I propose a new, market-based regulatory model for GM livestock that has both a strong scientific foundation and has worked for 10000 years. The model is similar to that for information technology in which specific algorithms drive computer and cell phone applications. Genome engineers write genetic algorithms that drive the traits in biological organisms. Accordingly, GM products should be viewed in terms of their use and public benefit rather than by limitations to the genetic programing coming from a few highly vocal groups. Genetic algorithms (Genapps) of the 21st century will include not only introduction of synthetic genes, but also complete natural and synthetic biochemical pathways to produce agricultural products that are maximally efficient, healthy to humans and animals, and sustainable in an era of changing climates while avoiding environmental degradation.
Globally, the area of land cultivated with genetically modified (GM) crops has increased a thousand-fold over the last two decades. Although this technology has become important for food production, the regulatory frameworks that underpin these outcomes are based on a list of requirements for a risk assessment that differ from country to country. In recent years, policymakers have had the opportunity to learn from the controversies over transgenics to create effective regulatory milestones for emerging technologies, allowing them to reach their potential for a more sustainable agriculture, ensuring food security. In Brazil, Law No. 11.105 of 24 March 2005 established a framework with four main organizations responsible for risk assessment and management. However, most of new breeding technologies did not exist at that time and were not considered in this law. In 2016, Normative Resolution No. 16 of the National Biosafety Technical Commission (CTNBio) was established to address this gap based on the evaluation of the products obtained through these techniques (termed Innovative Precision Improvement Techniques in the resolution), in a case-by-case consultation system. Briefly, if the product is designated to be a GM, the developer will have to go through the biosafety requirements and will be approved only after CTNBio risk assessment. If the product is designated not to be GM (for the purposes of the legislation), then it can be registered using the existing procedures. Currently, 152 GM products are commercially approved in Brazil. In 2018, CTNBio assessed the first consultation on commercial release of plants generated using the new breeding technologies and has subsequently approved six products. It is expected that many institutions would be able to participate in Brazilian and world markets, developing and introducing new biotechnological solutions and products through a more sustainable approach and without facing public disapproval, a common issue for GM crops.
The rapid development of biotechnology has provided a greater understanding of the biological functions of major candidate genes that have important functions regarding economic traits, and new materials for livestock breeding have been obtained through gene editing (GE) and embryo manipulation with the purpose of improving quality and output and reducing the costs and risk of disease. Public concerns, particularly over safety risks and production performance, must be addressed. Evaluation is the most important component of the regulation of gene-edited livestock and is a crucial guarantee of public safety before the marketing of gene-edited animal products. Here, the system of evaluation of gene-edited livestock is discussed in terms of public safety and production performance. The search for safe and ethical applications in the GE of livestock, a case-by-case evaluation strategy, and classification and simplification are used in order to promote a more efficient, objective, comprehensive and operable evaluation system.
Emergent coronaviruses (CoVs) such as SARS-CoV and MERS-CoV have posed great threats to public health worldwide over the past two decades. Currently, the emergence of SARS-CoV-2 as a pandemic causes greater public health concern. CoV diversity is due to the large size and replication mechanisms of the genomes together with having bats as their optimum natural hosts. The ecological behavior and unique immune characteristics of bats are optimal for the homologous recombination of CoVs. The relationship of spatial structural characteristics of the spike protein, a protein that is critical for recognition by host receptors, in different CoVs may provide evidence in explaining the coevolution of CoVs and their hosts. This information may help to enhance our understanding of CoV evolution and thus provide part of the basis of preparations for any future outbreaks.