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Forrest Innovations Aims to Use RNAi to Combat Citrus Disease, Control Mosquitos

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NEW YORK (GenomeWeb) – One of the co-founders of Beeologics — a developer of RNAi treatments for key bee disorders that was acquired in 2011 by Monsanto — has created a new business focused on using the gene-silencing technology to tackle a major threat to citrus crops and mosquito-borne diseases.

Called Forrest Innovations, the company was established by Nitzan Paldi, who in 2007 co-founded Beeologics to use RNAi to combat Israeli acute paralysis virus, a bee disease linked to colony collapse disorder, and the honey bee parasite Varroa destructor.

Monsanto continues to advance on the bee health programs. Following an 18-month stint at the ag-bio giant, Paldi left to start Forrest and explore the potential of RNAi to address two other key environmental issues.

Currently, Forrest has two initiatives underway. The first, dubbed Green Shield, is focused on stopping citrus greening, a disease that is believed to be caused by the Candidatus Liberibacter, a phloem-restricted genus of bacterium transmitted to plants by the Asian citrus psyllid. The disease has been reported in Africa, South America, North America, and Asia.

Notably, the damage caused by citrus greening isn't thought to be caused by the pathogen, but rather by the plant's defense response to infection, according to Paldi.

Likening the situation to a bee sting, which can lead to anaphylaxis in allergic individuals, Paldi said that "our hypothesis is that the bacteria elicits a kind of immune response from the tree, and the tree accumulates … molecules that block the phloem in the trunk and leaves."

This, in turn, impacts the translocation of nutrients in the plant, which affects the tree's ability to produce fruit and, ultimately, survive, he said.

In a sense, "what Forrest is doing is trying to [develop] the EpiPen of the tree," Paldi added. "We're trying to target specific components [of the tree's autoimmune system that] create this symptomatic response."

As for the actual gene targets of Green Shield, Paldi said that "if you go into the citrus literature, there is a lot regarding citrus greening including data associated with gene expression changes following infection. We are also generating our own proprietary data associated with gene expression patterns and changes over time associated with the infection process."

He declined to comment further.

Paldi also did not get into specifics about the delivery approach Forrest is taking with Green Shield. However, he stressed that the company is not modifying plants to express dsRNA — an approach being taken by other groups using RNAi for agricultural applications, such as Monsanto with its investigational corn rootworm-resistant corn strain Smart Stax Pro.

"It's always going to be topical and it's always going to be transient," Paldi said of Green Shield.

Currently, Green Shield is undergoing testing in a tomato model of citrus greening at Forrest's facilities in California, and is in greenhouse trials at its Brazil location in collaboration with the citrus growers group Fundecitrus.

Paldi did not provide a specific commercialization timeline for Green Shield, but said the he hopes it will hit the Brazilian market "soon" by using that country's regulatory approval process for fertilizers.

Forrest's second program, dubbed NoMoreMos, takes aim at mosquito-transmitted diseases such as malaria and dengue virus. Although such diseases are typically limited to less-developed nations, Paldi noted that mosquito control in general is big business.

"Florida alone spends over $140 million every year on mosquito control," he said. He also pointed to the recent $160 million acquisition of Oxitec, which is genetically altering insects to produce sterile offspring.

With NoMoreMos, the company is trying out three different approaches. In the first, it is using RNAi to downregulate undisclosed genes in mosquitos that enable their resistance to the widely used insecticide pyrethroid.

Paldi said this particular effort is fairly advanced and that Forrest anticipates beginning field trials in early 2016.

A less-advanced approach involves silencing genes that either increase or reduce mosquitos' resistance to the viruses that they transmit to humans. If resistance is increased, virus levels would be lowered to the point where they are no longer a threat. If it is decreased, infected mosquitos would themselves die from the infection.

Forrest's last NoMoreMos strategy uses RNAi to interfere with female mosquitos' reproductive process so that their eggs are not viable.

Despite the sale of Beeologics to Monsanto, Paldi said that Forrest is not looking to license or sell off its technologies.

"The target is to … develop products, to get them to the market, and be a product company because this is where the biggest potential upside is," he said.

Still, he added, "Forrest is a company and always acts in the best interests of its shareholders."

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