Block copolymer-dsRNA complexes for crop protection

The use of pesticides has allowed crop production to more than double over the last 60 years, reaching 9 billion tonnes in 2018 and keeping up with increasing food and plant-derived products demand due to population growth [1]. However, their excessive use has led to negative impacts on the environment and to human health and off-target species [1]. This has contributed to the development of alternative pest control measures that target only specific species while minimising off-target toxicity effects.

One such alternative is RNAi-based biopesticides that can be tuned to match specific pest genes and reduce the possibility of non-target damage. In this method, a double-stranded RNA molecule (dsRNA) is delivered to pests, stunting their growth or potentially causing pest death by selective gene silencing. Delivery vectors have been developed to protect RNA from degradation in the many environments it encounters before reaching the target sites within the pests. Recently a hydrophilic di-block copolymer has been synthesised for this purpose, where the cationic PQDMAEMA block binds to the negatively charged dsRNA and the neutral PDMA block provides steric stabilisation to prevent aggregation of the resulting polymer-dsRNA complexes, which were shown to effectively bind to and protect dsRNA [2].

In addition to protecting dsRNA, complexes should allow dsRNA release once within the pest's cells. To this end, this project will build upon the previously synthesised copolymer to include pH-responsiveness into polymer design. More specifically, both permanently quaternised (QDMAEMA) and pH-dependently quaternised (DMAEMA) monomers will be used to synthesise the cationic block. This block will then have a variable positive charge depending on the pH of its environment, which is expected to induce the triggered release of dsRNA under targeted conditions. Anticipated results include reproducing synthesis and characterisation techniques of previous polymers and complexes and testing a machine learning algorithm to relate polymer properties to complexes' performance based on collaborator data.

The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.