While mammalian delivery technologies are advancing to translation at an exceptional rate, delivery to plant tissues faces challenges, limiting their practical applications.
Crops genetically engineered for higher environmental stress and herbicide tolerance, enriched nutrition, disease resistance, and carbon sequestration for carbon management are important to meet global food demand. Gene editing technologies appear to promise faster and easier adaptation than traditional breeding approaches. However, to generate a desired genetic edit that is also transmitted across generations, the gene-editing machinery must be delivered to the appropriate plant tissue. In mammals, delivery systems have become increasingly sophisticated, with ongoing improvements in immunogenicity, targeting precision and efficiency1. Plants, however, have distinct physical barriers, have different transport systems (xylem and phloem) and are under continuous environmental stress. Mammalian delivery systems such as lipid nanoparticles (LNPs) are optimized for tissue-specific barriers2 and cannot traverse the plant cell wall. In addition, gene editing of human tissues is restricted to somatic cells to minimize safety concerns. In plants, the opposite is desired: for heritability, delivery systems must be capable of reaching reproductive tissues, or the editing reagents must be applied directly to these cells.
Growing plants for transformation takes time. The most common method is Agrobacterium-mediated transformation, whereby a natural pathogen transfers DNA containing an editing construct into a mass of undifferentiated plant cells called a callus. The callus can be screened for cells that have successfully been edited, and these cells can regenerate into a whole plant in appropriate culture conditions. Occasionally, other tissues such as the growing meristem or immature embryos can be transformed instead of a callus. As an alternative to Agrobacterium-mediated transformation, DNA has been attached to tiny gold particles that are physically propelled into plant cells through the cell wall and membrane, but DNA integrations using this method can be random, and many cells are damaged or die during the process3. Other approaches, such as viral delivery or regeneration of edited protoplasts that lack cell walls, rely heavily on tissue culture-based or transgenic intermediates, which are often time-consuming, labor-intensive, dependent on genotype and species, and bottlenecked by difficulties in plant regeneration or viral host range4.
The vast species variety of plants is another limitation. As in mammalian tissue delivery, what works well in one plant may not work in another. For plants, germline or meristematic tissues must be targeted, ideally in a species-agnostic way. Also, as in mammalian cells, edits need to be done efficiently, fast, and at scale.
Recent cell culture- and transgene-free “in planta” approaches avoid the time-consuming step of tissue culture for regeneration and have produced widespread interest in accelerating heritable editing. In these methods, developmental regulators are co-delivered with gene-editing reagents to induce new shoot meristems and enable heritable genome editing in whole plants5. Another recently published method grafts transgenic rootstocks to wild-type shoots to generate transgene-free offspring in one step6. While applications to tobacco, tomato, potato and grape (and in 2025 to soybean) have been successful, this crop-engineering workflow is not yet routine5.
Another recent in planta approach, virus-induced genome editing (VIGE), uses viral vectors to transiently deliver gene editing CRISPR components into plant cells directly, with high editing efficiencies and without the need for tissue culture intermediates7,8,9. Common viruses used for VIGE will not work for all plants, and currently the technology is not scalable. Whereas expanding the host range of mammalian viruses often requires altering cell entry viral receptor binding (tropism), broadening the host range of plant viruses may instead depend on overcoming constraints related to replication, systemic spread and host–virus molecular compatibility. VIGE approaches have worked well in dicot species, but their application in major monocot crops such as rice and wheat remains more challenging as a result of a more limited viral vector toolkit8. In addition, the virus must access the plant germline and deliver its payload to the meristem. It will be difficult to find a broadly applicable virus that can act on a wide variety of crops and cultured plants. Adding RNA mobility sequences can help to move the cargo, but not the virus10. Impairing plant immunity gives viruses better access to plant cells, and thus higher delivery efficiencies11, but plant-specific mechanistic and physical barriers are not easy to overcome.
Working with viruses as delivery technologies in plants also creates regulatory challenges. The use of infectious agents in the food supply requires rigorous demonstration that engineered viruses do not acquire unintended properties, harm non-target species or create new ecological risks. Addressing these regulatory concerns will be essential for broader adoption of such approaches. As an alternative, existing viral vectors with known safety risks could be engineered, with recognized engineering principles potentially adapted to broaden host tropism in plants.
Lipid nanoparticles (LNPs) have transformed the field of therapeutic genome editing in humans, but their application in plants remains far less developed. LNPs and virus-like particles are already known to carry larger editing machineries in mammalian cells, like those required for prime and base editing, and could be functionalized in plants. LNPs would need to navigate several barriers, including transport to the target tissue, passage through the cell wall, cellular uptake and intracellular cargo release. Nanosheets functionalized with lysozymes have been used to loosen the cell wall in target plants and deliver RNA cargo and plasmid DNA, demonstrating delivery to reproductive tissues (pollen) in tomato. Yet this was limited to GFP nucleic acid delivery; no editing machinery was delivered to enable heritable genome editing12.
Plant biotechnology companies seem to be striking a balance between investing in advanced transgene- and cell culture-free methods and more traditional routes of transformation. Terrana Biosciences is introducing engineered self-replicating, native plant RNAs into the plant that could move throughout the plant and deliver information or desired traits, avoiding the regeneration bottleneck of traditional methods. Synthetic latent RNAs can travel through the seed of corn, bell peppers and almond. Qi Biodesign is also looking at RNA-based grafting methods and alternative approaches including direct and transient protein delivery to the meristem in plants such as tomato. Vireo modifies plants directly in the greenhouse using shoot generation, also eliminating the need for tissue culture while still editing cells that can produce new shoots. Yet these technologies each need to be optimized with individual adaptions for every species and are not general solutions.
Considering the magnitude of the challenge and the benefits that time-saving advances could bring, the level of activity in plant delivery systems compared to that in mammalian ones appears modest. Of course, plant transformation approaches that perform efficiently in laboratory genotypes often show substantially reduced efficiency, or may fail altogether, when applied to elite commercial cultivars because of strong genotype dependence in transformation and regeneration processes. This could limit their wider adoption. But this is true for mammalian gene editing technology as well. Today, regulatory requirements for transgene-free approaches in plants vary between countries and are continually being modified to keep up with the pace of advances.
Gene editing in plants seems no longer primarily limited by the editing machinery itself, but by the ability to deliver it. If the field continues to improve the editor while leaving delivery largely unchanged, the practical reach of gene editing will remain limited by the biology of transformation. But if delivery becomes an equally deliberate target of innovation, the set of plants that can be engineered — and the traits that can be addressed — could expand dramatically.