Q3 2014 Bioclay Non-transgenic, safe and cost effective RNAi protection The Technology The need for new control agents for viruses, insect pests and diseases grows each year, driven by the need for greater production and climate driven pest and disease expansion. Viruses are one of the major plant diseases and responsible for about ~US$50b/annum production loss with few, if any, commercially available products available for their control. At the same time finding new modes of actions to combat pest resistance development is increasingly difficult, due in part to community and regulatory demands. The cost of developing a single new chemical crop protection agent is now commonly stated as being above US$250m. In this context, the use of RNA silencing (RNAi) plant defence mechanisms offers a significant opportunity to address crop protection needs. Research has demonstrated that the application of double stranded RNA (dsRNA) onto plants will confer viral resistance. Naked dsRNA can transfect plant cells when topically applied to leaf material and can infer protection against viral disease for up to 7 days (Gan 2010). The single biggest inhibitor to realising the full potential of the RNAi technology is the ability to deliver the dsRNA constructs into the plant cell and maintain its activity over extended periods of time. A Layered Double Hydroxide (LDH) nanoparticle has been developed at the University of Queensland that can load dsRNA (300-2000bp RNAi) to form a slow release capsule. This nanoparticle delivery mechanism gives a sustained, adjustable, slow-release of dsRNA to plants following topical application, giving viral protection. This technology opens the potential to combine a range of different, very selective RNAi control agents into one spray. Pepper Mild Mottle Virus Figure 1: Schematic representation of bioclay LDH-dsRNA nanoparticles dsRNA + Pepper Mild Mottle Virus Figure 2: Example of the power of dsRNA crop protection. The effect of dsRNA protection against pepper mild mottle Competitive Advantages Delivery of dsRNA into the plant cell Maintained, slow release of dsRNA over extended periods of time Nanoparticle comprises inexpensive material - cheap to produce at large scale Biologically benign dsRNA stable in LDH complex in storage Specific to target disease or pest Applications Delivery of dsRNA for plant protection. The first applications being pursued are for viral resistance and insect control. Significant opportunities exist beyond this. IP Position Manufacture: Composition: National Phase PCT Application Commercialisation opportunities UniQuest Pty Limited, the main commercialisation company of The University of Queensland seeks industry partners to license and co-develop this technology for specific applications. Contact name: Duncan Ferguson Phone: (+61) 407 733 619 E-mail: [email protected] People and Publications A/Prof. Neena Mitter The plant and microbial biotechnology group led by Dr Neena Mitter focuses on developing novel and innovative RNA silencing based biotechnological approaches towards management of biotic and abiotic stresses. The group were the first to show the breakdown of RNA silencing based resistance to plant viruses upon infection by a heterologous virus. The group is also investigating the potential of RNA silencing against fungi and insect pests and cutting edge platform technology for using artificial microRNAs for virus resistance. The diversity of expertise in her group across plant and animal science has led to collaborative project on nanoparticle based delivery of veterinary vaccines. Her current research projects include: RNA silencing based resistance to Phytophthora root rot of avocado ( Horticulture Australia Limited); Artificial microRNAs mediated resistance to viruses ( UQ and Washington State University); Discovery of microRNAs involved in high temperature tolerance in crop plants (Australia India Strategic Research Fund); Nanoparticle based delivery of veterinary vaccines (Queensland Government). A/Prof. Zhi Ping Xu A/Prof Zhi Ping (Gordon) Xu and his multidisciplinary research team have strengths in the controlled preparation of anionic clay nanomaterials, which have applications in drug, gene and protein delivery, and vaccinations. The team is developing a fundamental understanding of the interactions of clay-drug nanoparticles with proteins in serum and target cells, while also building knowledge of the subsequent biological effects. This understanding enables the design and synthesis of improved materials for a range of applications, including anti-restenotic drug delivery, gene delivery, protein delivery and vaccine adjuvants. The team and key collaborators cover a range of disciplines, which include nanomaterials science and technology, colloidal chemistry, cellular and molecular biology, biomedicine, immunology and neuroscience. Relevant Publications Zhao, Liang, Seth, Arjun, Wibowo, Nani, Zhao, Chun-Xia, Mitter, Neena, Yu, Chengzhong and Middelberg, Anton P. J. (2014) Nanoparticle vaccines. Vaccine, 32 3: 327-337. Mitter, Neena, Koundal, Vikas, Williams, Sarah and Pappu, Hanu (2013) Differential expression of tomato spotted wilt virus-derived viral small RNAs in infected commercial and experimental host plants. PLoS One, 8 10: e76276.1-e76276.14. Mody, Karishma T., Popat, Amirali, Mahony, Donna, Cavallaro, Antonino S., Yu, Chengzhong and Mitter, Neena (2013) Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery. Nanoscale, 5 12: 5167-5179. Bag, Sudeep, Mitter, Neena, Eid, Sahar and Pappu, Hanu R. (2012) Complementation between Two Tospoviruses Facilitates the Systemic Movement of a Plant Virus Silencing Suppressor in an Otherwise Restrictive Host. PLoS One,7 10: . Gu Z, Rolfe BE, Xu ZP, Campbell JH, Lu GQ, Thomas AC. (2012) Antibody-targeted drug delivery to injured arteries using layered double hydroxide nanoparticles. Adv Healthcare Mater 1, 669-673. Zhu Y, Li Z, Chen M, Cooper H, Lu GQ, Xu ZP. (2012) Synthesis of robust sandwich-like SiO2@CdTe@SiO2 fluorescent nanoparticles for cellular imaging. Chem Mater 24, 421-423. Li P, Xu ZP, Hampton MA, Vu DT, Huang LB, Rudolph V, Nguyen AV. (2012) Control Preparation of Zinc Hydroxide Nitrate Nanocrystals and Examination of the Chemical and Structural Stability. J Phys Chem C 116, 10325-10332. Gu Z, Rolfe BE, Thomas AC, Campbell JH, Lu GQ, Xu ZP. (2011) Cellular trafficking of low molecular weight heparin carried with layered double hydroxide nanoparticles in rat vascular smooth muscle cells. Biomaterials 32, 7234-7240. Bao HF, Yang JP, Huang Y, Xu ZP, Hao N, Wu ZX, Lu GQ, Zhao DY. (2011) Synthesis of Well-Dispersed Layered Double Hydroxide Core@Ordered Mesoporous Silica Shell Nanostructure (LDH@mSiO2) and Its Application in Drug Delivery. Nanoscale 3, 4069-4073. Wong YY, Markham K, Xu ZP, Chen M, Lu GQ, Bartlett PF, Cooper HM. (2010) Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles. Biomaterials 31, 8770-8779. Contact name: Duncan Ferguson Phone: (+61) 407 733 619 E-mail: [email protected]
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