Gene Editing of Wild Plants for Food Security
Modern Domestication of Crop Wild Relatives Through Multiplex Gene Editing for Climate-Resilient Agriculture
Agriculture today faces a question that is no longer limited to increasing yield in the field. A crop that performs well under normal conditions gains strategic value for food security only when it is also resilient to salinity, drought, disease, and climate variability. Modern crop varieties, through a long process of domestication and breeding, have acquired many market-desirable traits such as size, uniformity, and ease of harvest. Yet along the way, they have lost part of their genetic capacity to adapt to harsh environments. This is precisely where crop wild relatives become important, because they have survived in habitats where many commercial varieties are fragile.
Modern domestication, or de novo domestication, reverses the logic of plant breeding. In conventional breeding, the process usually begins with a cultivated variety, and wild traits are introduced through crossing and backcrossing; a pathway that can be lengthy and accompanied by linkage drag. In de novo domestication, the starting point is the wild or semi-wild plant itself, and domestication genes are edited in a targeted way so that part of the resilience capacity of the wild genetic background is preserved. This approach is especially important for crops that must remain agronomically effective in dry climates, saline soils, or the high-stress environments of the future.
– Hong Yu and Jiayang Li, researchers and authors of the Nature Communications article: “By the end of this century, a 50 percent increase in agricultural productivity will be needed to feed the world.”
The importance of this statement lies not only in the productivity figure, but also in the type of productivity required. Increasing production under conditions in which water, soil, and climate are becoming more constrained requires technologies that can both use natural genetic diversity and shorten breeding time. Multiplex gene editing, using tools such as CRISPR-Cas9, makes it possible to modify several genes or regulatory regions simultaneously, and this feature has turned it into a core technical tool in de novo domestication. For a country such as Iran, whose National Biodiversity Strategy and Action Plan reports an area of 164.8 million hectares and more than 8,200 recorded plant species, this is not merely a laboratory issue; it is tied to the future of food security, the water economy, and technological investment in the seed value chain.
How Does De Novo Domestication Change the Logic of Breeding Wild Plants?
In classical domestication, wild plants have been selected over many generations for traits such as non-shattering seeds, larger harvestable organs, uniform growth, flavor, flowering time, and compatibility with agricultural operations. This selection has formed the foundation of stable food production, but at the same time it has narrowed genetic diversity and eliminated many alleles useful for environmental stress tolerance. Crop wild relatives are a reservoir of alleles associated with drought, salinity, disease resistance, and climate adaptation, yet they are often unsuitable for direct cultivation. They may show seed shattering, late maturity, low yield, or poor market quality, and these features create the need for targeted redesign of domestication traits.
The main difference between de novo domestication and gene transfer is that it does not necessarily introduce a foreign gene into the plant. Many technical scenarios rely on editing endogenous genes or regulatory regions within the plant itself, with the aim of altering the expression pattern or function of genes that control domestication traits. Of course, depending on the delivery system, genetic constructs or transgenic systems may be used in intermediate generations and then Cas9-free generations may be selected through genetic segregation. This distinction matters for regulation, market acceptance, and the design of the commercialization pathway, because an edited line without foreign DNA may be assessed differently from a product that carries a stable foreign sequence.
De novo domestication is also not the same as single-gene editing. The goal of this method is usually to modify a set of traits simultaneously, because domestication is not a single trait; it is related to plant architecture, flowering time, fruit or seed size, nutritional quality, seed shattering, and agronomic adaptation. Scientific sources emphasize that turning a wild plant into a truly cultivable variety can take anywhere from several years to several decades, and in many cases requires dozens of genes, alleles, or subtle changes in gene expression. Therefore, multiplex editing can shorten the pathway, but it does not replace field evaluation, generational selection, or variety registration.
Multiplex Gene Editing in Wild Relatives: From Reference Genome to Field Testing
– The Reference Genome and Regeneration Bottleneck in Wild Species
The practical pathway of de novo domestication begins with selecting suitable starting material. Choosing a wild relative does not depend only on the presence of an attractive trait such as salinity tolerance or disease resistance; it also requires access to a reference genome, gene annotation, a regeneration system, and editability. Unlike model crops, many wild species do not have established tissue culture and transformation systems, and this becomes a technical bottleneck. A study on the allotetraploid wild rice Oryza alta showed that before trait improvement, the infrastructure for genome assembly, tissue culture, transformation, and genome editing had to be developed.
Once the infrastructure is in place, domestication genes or their homologs are identified in the wild species. At this stage, comparing orthologs with the cultivated species is important, because many genes controlling agronomic traits are already known in domesticated crops and can guide target selection in the wild relative. Editing target selection must balance two needs: reducing undesirable wild traits and preserving the very wild characteristics that made the starting material valuable in the first place. If this balance is lost, the project may produce a plant that appears more domesticated but has lost its original resilience value.
– Technical Metrics for Evaluating Traits and Generational Stability
Technical metrics in de novo domestication must be more precise than visual observation of the plant. The number of target genes and alleles, regeneration efficiency, the presence or removal of the Cas9 system, trait stability in subsequent generations, and performance across multiple environments are among the criteria that connect the laboratory pathway to variety development. For products generated through DNA delivery, selecting Cas9-free generations can be especially important for regulation and market acceptance. Trait stability is also not proven by observing a single generation; it requires multi-location and multi-year testing, genetic segregation analysis, and assessment of genotype-by-environment effects.
For stress-related traits, phenotyping becomes even more important. Tolerance to salinity, drought, disease, or heat must be measured using methods that are relevant to real production conditions. In wild tomato, the preservation of parental salinity tolerance after editing has been reported qualitatively, but for drought or salinity pathways at the level of a commercial variety, environmental, greenhouse, and field-based metrics must be designed from the beginning. The definition of water stress in World Bank and FAO AQUASTAT data also reminds us that water is not only a matter of rainfall volume, but the ratio of freshwater withdrawals to renewable water resources after accounting for environmental flow requirements.
Case Studies of Wild Tomato and Wild Rice in Demonstrating the Feasibility of De Novo Domestication
The first major demonstrative wave in this field was highlighted by two Nature Biotechnology studies in 2018 on wild tomato. In one of these studies, the wild tomato Solanum pimpinellifolium was used as the starting material, and multiplex editing was performed on genes and regulatory regions associated with plant architecture, flowering, fruit size, and vitamin C. The goal was for the wild plant to acquire some expected agronomic traits while preserving parental resistance to disease and salinity. The report of Cas9-free generations showed that this pathway can create a connection between trait improvement and reduced concern about the presence of the editing system in the final generation.
Another study on wild tomato, involving researchers such as Agustin Zsögön, Tomáš Čermák, Daniel Voytas, and Lázaro Eustáquio Pereira Peres, followed a similar logic. This study relied on the point that at least several important loci for domestication traits are known in tomato, including SELF PRUNING, OVATE, FASCIATED, and LOCULE NUMBER. The value of this case study is that it shows how genetic knowledge gained from the domesticated crop can be used to redesign a wild relative. This does not mean eliminating the breeding program altogether; rather, it makes the stages of discovery, targeting, and selection faster and more precise.
– Hong Yu, Tao Lin, Xiangbing Meng, Jiayang Li, and colleagues, authors of the Cell article on Oryza alta: “Here, a practical strategy, the de novo domestication of allotetraploid wild rice, is described.”
The example of the wild rice Oryza alta is important for another reason: it dealt with an allotetraploid genome and a more complex genetic structure. In the Cell study, an Oryza alta genotype with a CCDD genome was selected, and the researchers separated the genome assembly into two subgenomes, each with 12 chromosomes. Then, by developing tissue culture, transformation, genome editing, and genome assembly systems, six important agronomic traits were improved through editing homologs of known genes in diploid rice. This case study shows that de novo domestication in wild species is not simply a matter of choosing one gene; it depends on genome architecture, multi-target design, and the ability to manage polyploid complexity.
These three examples share one common message: multiplex editing can introduce domestication traits into a wild genetic background more quickly, but laboratory outputs should not be equated with ready-to-cultivate varieties. Even accompanying analyses on Oryza alta have stated that further genetic improvements are needed to turn edited lines into a commercial product. In tomato as well, the successful demonstration of preserving some traits from the wild parent does not mean that the market pathway is complete; evaluation across multiple climates, product quality, stable performance, and the regulatory route must still be completed. The value of these studies lies in proving technical feasibility, not in declaring the end of the variety-development process.
Conserving Crop Wild Relatives Is the Starting Condition for a Climate-Resilient Seed Economy
Without access to crop wild relatives, reference genomes, and phenotypic data, de novo domestication remains mostly an attractive idea. A regional review of West Asia and North Africa showed that the global CWR project assessed the conservation status of 1,076 crop wild relative taxa associated with 81 crops, and 95 percent of these taxa were underrepresented in ex situ conservation. About one-third of them had no ex situ seed samples at all. These figures show that the issue is not only gene editing; before editing, genetic material must be identified, conserved, documented, and made usable for research.
In the WANA region, actors such as ICARDA, Germany’s IPK, the United Kingdom’s Millennium Seed Bank, and national gene banks play roles in the conservation and use of CWRs. However, the same regional review attributes the difficulty of assessing national gene banks to the lack of public data, outdated data management systems, and uncertainty about sample quality. This situation sends a clear practical message for de novo domestication programs: germplasm must be transformed from a raw asset into a data-rich asset. A digital gene bank, records of phenotypic traits, habitat information, seed viability status, and genomic data are forms of infrastructure without which gene-editing technology becomes an unstable program.
In this framework, public-private partnership can support the pre-competitive stage, because CWR collection, reference genome production, and baseline phenotyping resemble quasi-public goods. Private investors usually enter when the product pathway, intellectual property, access to germplasm, and regulatory horizon are clearer. Public institutions, gene banks, and universities can reduce the initial scientific risk, while seed companies or technology investors can pursue the stage of converting a promising line into a marketable product. Without this division of roles, ambiguous costs, long development timelines, and regulatory risk can reduce the attractiveness of investment.
How Do Biosafety and NGT Regulations Shape the Market Pathway for Edited Varieties?
De novo domestication stands at the intersection of biotechnology, plant breeding, and biosafety regulation. Codex CAC/GL 45-2003, in assessing the safety of foods derived from recombinant-DNA plants, emphasizes comparison with the conventional counterpart and identification of new or altered hazards; this framework can also be used as a reference for the precautionary analysis of edited plants. The key issue is how the final product is evaluated in terms of composition, trait, and potential risk, not merely what the technology is called. Unintended effects are not unique to recombinant DNA and may also occur in conventional breeding, but safety assessment should reduce the likelihood of unforeseen adverse effects.
The European Union, in its proposed NGT regulation dated July 5, 2023, divides plants obtained through new genomic techniques into two categories. According to the European Parliament’s explanation, Category 1 plants differ from the parent plant by no more than 20 genetic modifications, and NGT plants remain prohibited in organic production. This categorization matters for de novo domestication because multiplex editing projects may require several genetic changes, and the boundary between categories can affect the regulatory pathway. Therefore, product design must be aligned with the regulatory map of the target market from the very beginning.
– Text from the European Commission document on the proposed NGT regulation: “Under this proposal, the prohibition remains in place for all NGT plants, food, and feed within its scope.”
Countries do not take a uniform approach, and this inconsistency becomes a market risk. In the United States, the SECURE rule was published in 2020, and APHIS described it as based on the characteristics of the organism rather than the method of production; however, on December 2, 2024, a U.S. federal court vacated the rule prospectively, showing that the regulatory situation can change over the lifespan of a project. Japan also determines the need for notification or safety assessment for foods derived from genome editing on a case-by-case basis. In such an environment, a de novo domestication program must be designed scientifically, legally, and commercially at the same time.
– Text from the document of Japan’s Ministry of Health, Labour and Welfare: “The need for notification or safety assessment is determined on a case-by-case basis by the Ministry of Health, Labour and Welfare.”
The United Kingdom has created a separate pathway for precision-bred plants and animals through the Genetic Technology Precision Breeding Act 2023. Argentina has also used a consultation approach since 2015 to determine whether products developed using new technologies are considered GMOs, and this approach has gained policy significance in Latin America. For a product that may be a seed, propagating material, or food derived from an edited plant, such differences are not merely legal issues; they directly affect time to market, compliance costs, labeling, exports, and collaboration with seed companies. For this reason, policy sensitivity must begin alongside genomic design, not after a promising line has been produced.
– Text from the UK Parliament document on precision breeding: “A bill to regulate the release, marketing, and risk assessment of precision-bred plants and animals.”
Iran’s Pathway for Localizing De Novo Domestication in Drought- and Salinity-Resistant Crops
In terms of plant diversity, Iran has significant initial capacity to enter de novo domestication programs. The National Biodiversity Strategy and Action Plan reports more than 8,200 recorded plant species and a large number of wild relatives of commercial species. This data does not mean direct technical readiness or the existence of a prioritized crop list, but it is important for justifying the stage of germplasm identification and the selection of native or regional CWRs. Crops such as cereals, legumes, forage crops, vegetables, and salinity-adapted plants can be examined at the research-policy level, provided that prioritization is based on germplasm data, climate needs, and the regulatory pathway.
Iran’s advantage in this pathway is not limited to germplasm resources; the relationship between this technology and the water economy and food security is also important. The definition of water stress in the World Bank and FAO AQUASTAT framework shows that pressure on water resources must be assessed systemically and cannot be solved simply by selecting one trait. Salinity- and drought-resistant varieties will not produce economic impact unless they are accompanied by yield, market quality, and farmer acceptance. Therefore, localization must be linked from the beginning to stress phenotyping, field testing in target environments, and assessment of agronomic value.
From a legal perspective, Iran is a party to the Cartagena Protocol, and the Biosafety Law of the Islamic Republic of Iran, dated July 29, 2009, defines a living modified organism as an organism with a novel combination of genetic material obtained through modern biotechnology. The executive regulation of the Biosafety Law, dated April 7, 2012, also regulates the production, release, transfer, export, import, and supply of genetically modified living organisms within an executive framework. For edited plants without foreign DNA, the exact decision-making pathway must be clarified based on official and case-by-case interpretation. This clarity is a prerequisite for reducing investment risk and preventing the project from stalling near the market stage.
– Text from the Cartagena Protocol on Biosafety: “Its objective is to ensure the safe use, handling, and movement of living modified organisms.”
Environmental risk in Iran must be viewed product by product. If an edited plant is compatible and crossable with native wild populations, gene flow and potential effects on biodiversity must be assessed before release. This issue is more sensitive in de novo domestication than in some other applications, because the starting material itself comes from wild relatives and may coexist with natural populations. Therefore, experimental field design, isolation distances, post-release monitoring, selection of test environments, and trait documentation must be part of the scientific program, not a secondary stage after laboratory success.
An Investment and Phased Implementation Framework for Variety Development Using Wild Relatives
From an investment perspective, de novo domestication should not be introduced with the promise of immediate returns. Existing sources do not provide a broadly valid and generalizable figure for the capital or operating cost of this type of program, and this makes decision-making dependent on precise phasing. The first stage should be pre-competitive and should focus on germplasm mapping, crop prioritization, reference genomes, annotation, stress phenotyping, and the establishment of regeneration systems. Only after passing through these bottlenecks can multiplex editing, selection of stable generations, and field testing move closer to a commercial program.
The appropriate implementation model is a combination of public and private roles. The public sector and universities can strengthen baseline data, digital gene banks, stress-testing infrastructure, and the biosafety framework. Knowledge-based companies and technology investors can contribute to construct design or delivery systems, production of edited lines, high-throughput phenotyping, pre-multiplication greenhouses, and the market pathway. This division of labor is compatible with the mission of holdings active in knowledge-based agriculture, biotechnology, value chains, and modern financial instruments, because economic value is created through the connection between technology, data, regulation, and market access.
Iran’s decision-making pathway should begin with several practical questions. Which crop has higher priority in terms of food security and water pressure; which wild relative is accessible, documented, and editable; which domestication traits must be targeted simultaneously; and what regulatory framework governs the domestic or export target market. Precise answers to these questions prevent the technology from becoming a purely laboratory-based project. De novo domestication gains economic value when it is designed from the beginning around the seed value chain, farmer needs, target climates, biosafety, and the pathway to market acceptance.
The Future of Climate-Resilient Varieties Through the Link Between Wild Germplasm and Gene Editing
De novo domestication of crop wild relatives is not a simple answer to the crises of drought and salinity, but it is one of the serious scientific pathways for bringing genetic diversity back into breeding programs. The strength of this approach is that it begins with a wild genetic resource and seeks to introduce domestication traits without completely eliminating natural resilience. Its limitation is also clear: every wild species requires a reference genome, an editing system, stress phenotyping, field testing, safety assessment, and a regulatory pathway. Therefore, its success is not measured by one successful edit, but by the conversion of a set of scientific and operational infrastructures into a stable variety.
For Iran, the value of this technology lies at the intersection of three areas: biodiversity, climate-resilient agriculture, and technological investment. The existence of abundant plant species and wild relatives of commercial species is an important starting point, but it is not sufficient. The practical pathway must begin with germplasm documentation and crop selection, continue with genomics and phenotyping infrastructure, move within a clear biosafety and regulatory framework, and eventually lead to a variety that can be tested in the field. Such a pathway can shorten breeding time, but it will contribute to food security and the seed economy only when science, regulation, market access, and biodiversity conservation are considered simultaneously.
