Open-Source Initiative Circumvents Biotech Patents

A CORE TECHNOLOGY

BioForge's flagship technology is Trans-Bacter, a new technique for gene transfer to plants, which scientists developed at CAMBIA and described in February in Nature.¹ The technique is novel because it relies on bacterial species other than Agrobacterium tumefaciens, a commonly used gene-transfer tool covered by patents held by a number of large biotech companies including Syngenta and Monsanto.

In nature, Agrobacterium induces galls in plants by inserting a portion of a tumor-inducing (Ti) plasmid into a plant cell. This so-called transferred DNA (T-DNA) then integrates into the host genome. Agricultural scientists have exploited this mechanism, deleting oncogenes from the Ti plasmid and substituting transgenic genes that endow plants with the ability to resist herbicides or generate nutrients.

The CAMBIA team removed the T-DNA locus from a Ti plasmid isolated from a virulent strain of Agrobacterium. The researchers then introduced the T-DNA into three non-Agrobacterium strains, along with a novel plasmid containing a new T-DNA sequence, and GUSPlus, a new BIOS-licensed reporter gene that permits sensitive visualization of gene-transfer events. They found that each species could transfer genes to a variety of plant types, including tobacco, Arabidopsis, and rice, with varying levels of efficiency.

Steven Hughes of the Center for Genomics in Society at the University of Exeter, UK, notes that the CAMBIA research has implications for the understanding of horizontal gene-transfer events, as it demonstrates that several bacterial species can transfer genes to an organism outside their phylogenetic kingdom. "Agrobacterium was assumed to be the only organism with that potential," Hughes says.

More broadly, TransBacter was developed with the intent to fall outside the scope of existing patents. As the authors note, the majority of patents covering gene transfer to plants refer specifically to Agrobacterium as the transfer medium and not to the segment of DNA actually responsible for transferring the gene of interest. "By analyzing these patents, we found an Achilles' heel, which is that their definitions of the properties are restricted to the tumefaciens species or the Agrobacterium genus," says Jefferson, who notes that BIOS is not restricted to agriculture or even biotechnology but can be applied broadly to all types of biological innovation.

It's too early to know whether academia and industry will embrace the BIOS model. Plant geneticists in the public sector will likely be interested in the approach, says Steven Strauss, professor of forest science at Oregon State University in Corvallis. "We feel [that] unless there's something like an open-source alternative, we're just disenfranchised."

But, University of Arizona plant geneticist Richard Jorgensen notes that for many academics using proprietary technologies for research purposes, patents are not an issue because most large biotech companies don't enforce them in such cases. "The average scientist will probably have to be convinced; they may not jump at it," says Jorgensen. "But I would think anyone in a smaller company, smaller entities that don't want to be controlled by large ag-biotech companies, would be really enthusiastic about participating in something like this, because it's their ticket potentially to independence."