Gene editing has advanced rapidly over the past decade, but commercial deployment in crops has lagged behind expectations.
According to BetterSeeds, a plant biotech company developing advanced gene‑editing delivery systems, the science of editing itself is no longer the primary limitation. Instead, the bottleneck increasingly lies in how editing tools are delivered into plants and regenerated into fertile, commercially viable varieties.
A newly announced collaboration between BetterSeeds and Caszyme, a specialist in CRISPR‑Cas molecular tools, is designed to address that constraint head‑on.
The partners will work to integrate Caszyme’s ultra‑compact Cas12l nuclease with BetterSeeds’ proprietary EDGE™ (Efficient Delivery of Gene Editing) platform, which uses engineered, deactivated plant viruses as delivery vectors. Together, they aim to eliminate or dramatically reduce the need for tissue culture – long regarded as a major bottleneck because it is often time-consuming, costly, and prone to low regeneration success.
The focus is not just on better editors, but on fixing the delivery problem. Tissue culture has become the “default” operating system for plant editing, said Ido Margalit, CEO of BetterSeeds, but it was never designed to support scalable, commercial deployment across diverse crops and breeding programs.
Why tissue culture remains the biggest constraint
Tissue culture plays a central role in most plant gene‑editing workflows. Edited cells must be regenerated into whole plants, typically through lab‑intensive protocols that vary widely by crop and genotype.
According to Margalit, this creates multiple layers of friction. “Tissue culture is a bottleneck at multiple levels,” he said. “It is slow, labour‑intensive and highly genotype‑dependent. A protocol that works in one variety often fails in another, even within the same crop.”
Regeneration itself is also unpredictable. Attrition rates are high, timelines are long, and success is difficult to guarantee. For many mid‑sized and smaller seed companies, that uncertainty is compounded by a lack of infrastructure, specialist staff and capital.
“In practice, even when the editing chemistry works, the path to a commercial plant becomes too slow, too expensive and too crop‑specific to scale,” Margalit said.
Viral delivery shifts the editing workflow
BetterSeeds’ EDGE platform is built around a different assumption: that gene‑editing tools can be delivered biologically, rather than through regeneration‑heavy cell culture processes.
Using engineered plant viral vectors, EDGE is designed to carry CRISPR components directly into plant tissues. That approach fundamentally changes the architecture of the editing workflow.
“Instead of depending on tissue culture as the central operating system of editing, we shift delivery into the plant itself,” Margalit said. “The result is a simpler workflow with fewer artificial steps, fewer points of failure and timelines that are much more compatible with real breeding programmes.”
Rather than eliminating tissue culture entirely, EDGE aims to make it optional in most use cases.
“In many crops and workflows, we substantially reduce dependence on tissue culture,” Margalit told AgTechNavigator. “When it’s still required because of plant physiology, we confine it to a much smaller and more manageable part of the pipeline.”
Why compact Cas12l nucleases matter
Viral delivery is not a new concept in plant biotechnology, but historically it has been limited by the size of first‑generation CRISPR tools such as Cas9. Plant viruses have strict cargo limits, making large nucleases difficult, or impossible, to package and transport efficiently.
According to Margalit, this is where Caszyme’s contribution becomes critical.
Caszyme has optimised a Cas12l mini nuclease, originally discovered and owned by Corteva Agriscience, which is significantly smaller than first‑generation editors. Corteva has licensed Cas12l to both Caszyme and BetterSeeds for further development and integration.
“Compact nucleases such as Cas12l are far better suited for viral delivery than Cas9, which is simply too large,” Margalit said. These are not just smaller versions of older tools, he stressed, “they enable delivery strategies that were far less feasible with first generation CRISPR systems.”
By integrating Cas12l into EDGE, the partners aim to deliver ultra‑precise editing cargoes that fit within viral vectors without compromising editing efficiency.
Precision without tissue culture
One concern often raised about non‑traditional delivery approaches is whether they sacrifice precision or reproducibility – a premise that Margalit rejects.
“Precision comes from the nuclease, guide design and molecular architecture – not from tissue culture,” he said. “Tissue culture is just a means of introduction. It does not inherently make the edit more accurate.”
According to Margalit, Cas12l delivers precision comparable to – and in some cases on par with – first‑generation editors, while viral delivery improves consistency of introduction.
“Reproducibility is addressed through vector engineering, controlled delivery design and crop‑specific optimisation,” he said. “We’re not replacing control with randomness. We’re replacing an inefficient delivery bottleneck with a biological system that can be engineered and standardised.”
Scaling without scaling lab infrastructure
The implications become more significant once editing moves beyond the laboratory.
“Tissue culture scales poorly,” Margalit said. “It requires dedicated facilities, trained personnel and custom regeneration protocols for each crop and genotype.”
By contrast, viral delivery removes much of that fixed overhead.
“For seed companies, that can translate into materially lower costs, substantially shorter development cycles and the ability to run far more editing programmes in parallel,” he said.
BetterSeeds estimates that viral delivery‑based workflows could reduce time and cost by more than 50% compared with traditional, tissue‑culture‑heavy approaches, while expanding the range of crops and genotypes that can be edited.
Lower barriers for seed companies
Beyond speed and cost, BetterSeeds sees adoption as a central challenge.
“Most seed companies do not want to become tissue culture companies or build large gene editing infrastructure from scratch,” Margalit said.
The company aims to offer editing, delivery and traits as an integrated package that can plug into existing breeding pipelines with minimal new infrastructure.
“The objective is to make advanced editing usable in‑house by a much broader part of the seed industry,” he said.
Moving the bottleneck upstream
If tissue culture ceases to be the dominant constraint, Margalit believes the next limits will be more strategic than technical.
“The bottleneck moves from “Can we make the edit?” to “Which edits create real agronomic and commercial value, and how fast can we move them through breeding and market channels?”
He sees that shift as a sign of maturation. “It means innovation is no longer held back mainly by lab mechanics, but instead by the strategic work of choosing the right traits, validating them and deploying them at scale,” he said.
Over the next five years, Margalit expects tissue culture to evolve from a default requirement to a specialised tool – used where necessary, but no longer universal.
“If delivery systems like ours continue to mature, gene editing becomes faster, cheaper and far more accessible,” he said. “That has the potential to democratise innovation across crop genetics.”
Dr Giedrius Gasiunas, CEO of Caszyme, said the collaboration creates a new pathway for agricultural innovation.
“Cas12l performs very well in crop genome editing,” he said. “By combining our platforms, we are not just advancing technology, we are creating a new pathway for agricultural innovation that can lead to more resilient and sustainable crops.”
