RNA therapeutics have huge potential to effectively treat a diverse range of diseases (including some that are otherwise “undruggable”) with high specificity and potency. However, the major limiting factor for their further success remains the lack of effective systems for systemic delivery of RNA therapeutics to specific diseased cells. Sixfold Bioscience is addressing this challenge through their modular RNA delivery system, MergoⓇ, which can be functionalised with therapeutics and targeting molecules that recognise biomarkers on specific cells of interest and not others. First-generation siRNA-MergoⓇ demonstrated promising in vitro and in vivo results, with highly competitive safety and favourable cost profiles. This project aimed to package mRNA and bioconjugate it with MergoⓇ, in order to diversify the therapeutic cargo possible to be delivered by MergoⓇ to cells.
The overall objectives of this project were:
Recruitment, integration and training of an Innovation Associate with the necessary expertise to complete the project to a high standard, and add knowledge value to our SME.
Generation of multiple MergoⓇ versions for further in-house in vitro and in vivo characterisation.
Development of bioconjugation and packaging methods for mRNA delivery.
Protection of IP generated during the grant through patent applications.
Conclusions of the action:
The Innovation Associate was recruited and completed his training (to the extent which was possible, given travel restrictions from the covid19 pandemic). Additional internal training was provided, covering Project Management and Prioritisation, Leadership, Grant Writing and Health and Safety.
All project objectives were fulfilled, however these were performed on shorter RNA strands and served as the groundwork for additional follow-on studies.
Additional work to synthesise, optimise and conjugate endosomal escape peptides (important to increase drug availability in the cell’s cytoplasm) was also completed.
IP has been filed to protect the bioconjugation strategies and peptides established and validated in this project.
