RNA nanotechnology for rapid and sustainable preclinical iteration of gene therapeutics

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While traditional pharmaceutical development of small-molecule and protein-based therapeutics can take years to reach patients, a more agile multi-disciplinary approach based on gene therapies has the potential to not only reduce time to market, but also improve therapeutic outcomes and reduce cost. This ability to rapidly engineer gene therapies has been clearly demonstrated during the outbreak of COVID-19, whereby several of the leading SARS-CoV-2 vaccine candidates are utilising mRNA, a form of gene therapy. However, in order to better respond to rapidly emerging viral infections such as COVID-19 and develop more targeted and personalised approaches for the treatment of cancer and genetic disorders, there is a need for a more adaptable approach to the delivery of gene therapies. Current approaches for the delivery of gene therapies, include conjugation, lipid nanoparticles or viral vectors. However, the exploitation of these delivery technologies for diverse indications has been impeded by the limited targeting specificity of diseased cells, toxicity and/or the lengthy and expensive manufacturing process. Sixfold's patented Programmable Oligonucleotide Delivery System (PODS) has been engineered as a rapidly scalable, non-toxic and targeted approach for the delivery of gene therapies. The technology has been validated in vitro and in vivo mammalian systems, showing favourable safety and biodistribution. The technology is unique in that it allows gene therapies to be simply 'clicked' onto their PODS enabling rapid iteration and short design-to-manufacture lead times.The **two objectives** of this project are to introduce a more **rapid development cycle** for fast iteration and introduce a significantly more **sustainable development process from manufacturing through to testing**. The innovative approach outlined in this project seeks to reduce the lead times from the current 24 weeks to 6 weeks, which will allow for a more rapid response to emerging infectious diseases AND the parallel development of gene therapeutics across multiple disease indications. This project will focus on doing this in a more environmentally sustainable way. By partnering with Pharmidex, a leading UK CRO offering in silico and in vivo services, we can reduce our wet lab work and limit the use of animals to only essential studies by using their in silico methodologies for candidate selection and their cascade approach to funnel the best candidates into efficacy testing. Sixfold will also overhaul the manufacturing process reducing reagent consumption and waste, and increasing yield, as well as taking on a more high-throughput approach to in vitro testing which will further reduce plastic waste and the use of animal-derived reagents.The success of this project will make Sixfold world leaders in drug delivery system development times through the introduction of a more agile development methodology into their process and allow Pharmidex to develop a more comprehensive suite of in vivo experimentation services including an expansion into oligonucleotide-based therapeutics.