RNAgri technology allows RNA to be manufactured using well proven large scale fermentation processes. Prior to RNAgri manufacturing innovations, these large scale fermentation processes were not viable because the RNA produced was almost immediately destroyed by microbial nucleases. The resulting low RNA yields resulted in RNA costs that were prohibitive for uses in agriculture.

RNAgri technology uses a protein to bind the RNA as it is produced, thus protecting it from RNAse degradation. This protein protects the RNA allowing subsequent isolation and purification. There is also a high level of interest in using the protein bound RNA as a delivery mechanism.

The adjacent video provides a basic overview of how RNA interference (RNAi) works.

Potential for RNAi Technology

Agriculture

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RNAgri - three plants icon

Pests

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Additional

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Status and Benefits of RNAi Technology

RNAgri - RNA icon

Status

RNA interference (RNAi) is a natural phenomenon ubiquitous to all eukaryotes (Animals, Plants, Fungi and others). RNAi occurs when small stretches of RNA inhibit gene expression mainly by interfering with the function of “messenger RNA”.

Discovered about 15 years ago, RNAi is considered a recent major breakthrough in biological science. In 2006, Andrew Fire and Craig C. Mello shared the Nobel Prize for this discovery published in 1998!

There are two fundamental problems with RNAi approaches as a practical matter, however:

  • One is the high cost of making RNA. This high-cost puts RNAi well out of reach for the vast majority of its potential product applications, especially in agriculture.
  • A second fundamental problem is the effective delivery of RNA to the target tissue within the target organism. Precisely because RNA is potentially so powerful, most life forms have developed one or several defense mechanisms to protect themselves from exogenously produced RNA, most importantly enzymes called “RNAses” that cut up or otherwise destroy exogenously produced RNA on contact.

RNAgri’s core technology addresses both of these problems and has the potential to change the industry.

Benefits

There is enormous interest among life-science researchers across many disciplines in RNAi as a tool for research and as the basis of life-science products offering a wide range of potential benefits. RNAi activity resulting from topically applied RNA promises the ability to control gene expression in a highly targeted way without genetically modifying the target organism.

Unlike traditional life-science products, RNAi works in such a specific way – typically targeting a single gene – that it promises the ability to promote highly specific and desirable biological effects with greatly reduced “off target” effects. This might include insecticides that target only crop pests and which have no effect on benign and beneficial insects; and new non-GMO approaches to boost agricultural productivity without having to make genetic alterations to the genome of the crop plant.

RNAgri Offerings

Technology

RNAgri’s approach (patents pending) allows our licensees and partners to make RNA using large-scale fermentation approaches greatly reducing the cost to produce these valuable natural products. Our approach is based on binding the RNA, as it is produced inside a microbe, to a protein that protects RNA from degradation by RNAses during the fermentation process. This RNA proten complex can also provide a stable delivery mechanism protecting RNA from RNAses in the environment – and from other environmental hazards such as UV light. The RNAgri approach holds promise of effective delivery of RNA to where it can have its desired biological effect.

RNAgri - spray plants icon

Products

  • Enabling Low- Cost, Commercial Scale Manufacturing:

    Once validated lead RNAi constructs are identified, RNAgri scientists engineer these constructs to be prepared using commercial scale fermentation in gram-negative and gram-positive bacteria and yeast.This involves engineering microbes to produce specific protective proteins and engineering the RNA to contain specific sequences that will bind to these proteins. These RNA-protein complexes make the RNA stable to nucleases in the microbe that would normally degrade the RNA.
    This proprietary technology allows large amounts of RNA to accumulate in the microbe. This RNA can then be isolated for use or in some cases the microbes (usually non-viable) can themselves be used for application.This technology is very simple and, because it uses tried and true fermentation processes, is scalable to enormous industrial volumes. Microbes are co-transformed with these plasmids coding for the binding protein and the target RNA. As these microbes multiply in culture they simultaneously produce the protein and RNA which self assemble.
    The protein-RNA complex is stable to nucleases and the target RNA accumulates. Subsequent processing can remove the protein to create pure double strand RNA or the protein-RNA complex can be left intact to potentially enhance stability from environmental nucleases. This technology leverages well understood fermentation processes that have been utilized at massive scale for decades.

 

  • Optimizing RNAi Delivery Modality:

    RNAgri technology facilitates the production of RNA by using a protein-RNA complex to protect the RNA from degradation by nucleases. In some cases, the RNA-protein complex forms a capsid in which the RNA is completely enveloped and sequestered by the binding protein.One of RNAgri’s most compelling advantages as a platform for the
    in-field delivery of exogenous RNAi is the protection provided by this encapsidated RNA from the environmental degradation of RNA. RNAgri has identified numerous protein constructs, all covered by RNAgri’s patent estate, which may naturally facilitate uptake by plant and insect cells, and which could be explored to maximize delivery of RNAi to selected target organisms.

 

  • RNAgri Patent Estate and Freedom to Operate:

    The RNAgri IP portfolio covers dsRNA production in gram-negative and gram-positive bacteriaand yeast. RNAgri is filing patents regularly including refinements to its methods as well as specific RNA sequences for the specific control of ant species including fire ants and
    the numerous species of household ants.Further IP will include RNA sequences specific for cockroaches and termites. RNAgri has been granted two U.S. patents and has 8 U.S. and
    international patents pending. One international patent has been granted in Japan. RNAgri has filed for patents in the following countries: Argentina, Australia, Brazil, Canada, China, European
    Union, Hong Kong, Israel, India, Japan, Mexico, Singapore and the United States.RNAgri has commissioned a third party IP review that shows a solid and protectable intellectual property estate as well as unfettered freedom to operate. A table with all RNAgri published patents is shown below.

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