The Consortium

Work Package 1 will generate and develop a wide range of novel NAT compounds to be studied in in-vitro and in-vivo experimental systems.

This work package is led by Prof Tom Brown from Oxford University, who brings top chemistry expertise in nucleic acid chemistry and NAT conjugate technology. Working alongside partners from leading academic centres outside of the UK (Prof Anastasia Khvorova at the University of Massachusetts and Prof Samir El-Andaloussi at the Karolinska Institute) as well as commercial organizations at the forefront of NAT conjugate drug development (AstraZeneca, Silence Therapeutics), these strong academic-industry partnerships will add significant contributions in the form of compounds and expertise.

Work Package 2 will utilise cell-based assays for NAT screening which will provide key mechanistic data on the molecular rules governing “productive” NAT uptake, trafficking and toxicity in-vitro, and how alterations in NAT chemistries/delivery systems can be positively modulated.

Work Package 2 is led by Prof Anne Willis, Director of the MRC Toxicology Unit at Cambridge University and expert in the development and use of cell-based assays for NAT screening and drug development. 

Work Package 3 will establish ex-vivo human translational systems to test novel oligonucleotides in CNS model systems, including primary cells, iPSCs and organoids.

Work Package 3 is led by Prof Sarah Tabrizi, UCL, a world-leader in pre-clinical development and delivery of first-in-human clinical trials of novel NAT for Huntington's disease (HD).

Work Package 4 will perform translational in-vivo studies in wild-type and reporter rodent systems to investigate CNS and heart/muscle NAT delivery, biodistribution, efficacy and safety.

Work Package 4 is led by Prof Matthew Wood from Oxford University, who brings expertise in developing RNA-based medicines for neuromuscular diseases as well as using rodent model systems for NAT drug development. As well as directing the TransNAT consortium, Professor Wood is Director of MDUK Oxford Neuromuscular Centre and the Oxford Harrington Rare Disease Centre. This work package will work closely with the Mary Lyon Centre at MRC Harwell on the generation of novel NAT reporter models.

Work Package 5 will utilise clinically relevant disease models of Huntington’s disease (HD) and Duchenne muscular dystrophy (DMD) to test and validate select lead NAT compounds.

Work Package 5 is led by Prof Francesco Muntoni, who is a leading expert in antisense therapy development for CNS and muscle diseases (including HD and DMD), as well as preclinical to clinical translation of NATs to first in human trials.

Work Package 6 will develop artificial intelligence and machine-learning methods for the prediction of NAT conjugate cellular properties through novel data and computational analysis. This work package is led by Prof Heba Sailem, Head of Biomedical AI and Data Science at King’s College London and a pioneer in the concept of Knowledge-Driven Machine Learning which has been widely adopted in the field as an effective way of interpreting large data.

Work Package 7 The consortium is managed by the Governance work package, comprised of 3 groups that work together to provide the framework and support needed for the successful delivery of the programme:

The Consortium Delivery Group, a key-decision making team responsible for developing and managing the implementation of the TransNAT Programme, chaired by the programme Director Prof. Matthew Wood and including Work Package Leads, the TransNAT Programme Manager, as well as NATA and the Commercialisation Committee lead.

The Commercialisation Committee, supports the translational strategy, commercialisation aspects and management of intellectual property. Chaired by Dr Deepak Kumar from the Oxford University's Translational Research Office, it includes representatives from each participating organisations' Technology Transfer Office, plus the senior leadership team. 

The External Advisory Board, chaired by NATA Executive Director Prof Nick Lench and a team of external advisors experts in the field of Nucleic Acids Therapies.