The National Therapeutic mRNA Platform integrates pivotal patents and internationally leading expertise in mRNA protein output rates, CRISPR RNA editing, RNA structure and modification detection, and AI-driven RNA design for streamlined product development. With a co-design strategy involving community groups, the NTRP targets maximal impact across diverse therapeutic needs. 

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Innovative technologies

The platform develops and implements innovative experimental and computational methods to optimise mRNA for key therapeutic aspects such as stability, activity, structure, and cell specificity, leveraging foundational research on RNA function and technologies:

• Functional characterisation of RNA processing,
• Translatability and Chemical modification profile,
• Computational biology and AI to study RNA,
• High-throughput screening and Synthetic biology-based approaches

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AI-based generation and optimisation of therapeutic RNA designs

• Training and testing of predictive models to generate optimal RNA molecules
• Design of new mRNA scaffold candidates containing variants in the nucleotide sequence and modifications, within the constraint of maintaining the encoded protein for the specific therapeutic application (e.g., antigens, peptide inhibitors), and optimising for improved stability, translatability, and low risk, using the measurements from our comprehensive datasets.

Modelling therapeutic risk

• Prediction of cell toxicity of RNA candidates and scoring them for safety to develop mRNA therapies with low-risk profiles.
• AI are used to integrate information from diverse sources to understand the interactions between mRNA therapeutics and cellular response.
• Genotoxicity prediction of the delivery vector
• Models for mRNA therapeutic risk based on the impact of RNA substitutions on translation and the potential use of other biomimetic replacements.

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mRNA performance measurement

• Novel technologies integrating AI-based algorithms with state-of-the-art live cell profiling methods to measure mRNA protein translational capabilities within a given cell type,
• Best accuracy in vivo translation definition and dissection of translation mechanism
• Approaches to further enable dissection of translation mechanisms, RNA integrity, and accurate single-molecule quantitative detection of RNA modifications, including 5-methylcytosine (m5C), N6-methyladenosyne (m6A), and pseudouridine, outperforming competing technologies.
• Existing instrumentation to provide accurate transcriptome-wide measurements of mRNA performance (e.g., translation, stability, and localisation) in cells and organoids closely matching the target of therapy, primarily using short- and long-read high-throughput sequencing technologies, as well as other analytical methods.

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High-throughput testing of RNA candidates

• Cell-free, Cells, and organoids, for the validation of RNA products.
• Wide selection of assays customised to the type of therapeutic, the desired function of that therapeutic, and the disease and/or disease model to be tested.
• mRNAs are complexed as lipid nanoparticles (or extracellular vesicles) or delivered via nucleofection into cells in high-throughput microplate format.
• Cell function and/or phenotype are monitored using a suite of high-throughput equipment, including microplate biochemical readouts, flow cytometry, and high-content imaging analysis.

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