Establishing a National Platform for the Development of Nucleic Acid Therapy for Rare Disease

Nucleic acid therapeutics (NATs) offer great potential to treat rare diseases (RDs) by addressing their genetic causes in a target-specific manner. The exponential increase in NAT clinical trials in the last few years clearly demonstrates the role of these molecules in translational research and unique opportunities for investigator-led preclinical and clinical studies, in which the UK has particular track record strengths.

To further promote the development of NATs for RD patients in the UK, we are creating the node entitled, 'Establishing a UK Platform for the Development of Nucleic Acid Therapy for Rare Disease' (UPNAT). UPNAT will bring together relevant stakeholders, comprising of scientists, clinicians, geneticists, trainees, patient advocacy groups and charities, industrial partners, international non-profit organizations and regulatory bodies, to establish and coordinate a national network that will facilitate the exploitation of the rapid development of NATs.

UPNAT intends to address a number of challenges that NAT research and development is currently encountering in the RD field within the UK, including 1) a lack of a national infrastructure for cross-disciplinary knowledge exchange and expertise sharing between centres leading NAT preclinical and clinical development; 2) a clear path for systematically linking patients carrying unique mutations to NAT expertise; and 3) the need for continuous dialogue between regulators and researchers to streamline the process of regulatory approvals, monitoring of outcomes, and accelerating the clinical translation of RD-specific NATs.

To tackle these challenges, UPNAT will create the following networking opportunities: 1) scientific symposia to promote cross-disciplinary knowledge exchange between researchers, clinical and industry stakeholders; 2) webinars and activities between patient advocacy groups, charities, and researchers to promote public engagement; 3) training schemes to educate and equip the next generation of scientists and clinicians with the knowledge and skills to lead future NAT research programs.

The node encompasses three complementary projects, to address the overall objectives and crucial bottlenecks. These projects focus on 1) Target selection, NAT strategy design and pre-clinical development; 2) Enhancing UK's capability in NAT scale-up synthesis and pilot toxicology studies tailored for RD; 3) NAT clinical trial design and regulatory approval.

Collectively these work packages will enable a robust framework for the design, development, and clinical translation of NAT to be adopted by RD centres in the UK.

UPNAT will focus on areas of unique strength in rare paediatric and adult disorders, including six paediatric highly specialised services provided by the partner organisations in London, Oxford, Cambridge, Birmingham, Liverpool and Sheffield, and the adult expert centres at the University College London (UCL) Institute of Ophthalmology, Institute of Neurology, Moorfields Eye Hospital and University College Hospital. The node will be focused on neurological, neurodegenerative, metabolic and ophthalmological diseases which are uniquely conducive for NAT applications and remain open to other disease areas as NAT technology rapidly advances and Node develops.

UPNAT will be led by investigators and collaborators from UCL Great Ormond Street Institute of Child Health, Institute of Ophthalmology, Institute of Neurology, Great Ormond Street Hospital (GOSH), Moorfields Eye Hospital, UKRI NATA (Oxford) and investigators from Oxford, Cambridge and Birmingham. Node members will work in partnership with Genomics England, five NIHR BRCs (GOSH, UCLH, Moorfields, Oxford and Cambridge), industry, patient advocacy groups and charities, the UK regulators, and the international consortia on NAT in RD.

Collectively, we are well equipped and determined to maximise the transformative potential NATs offer for the RD patient community within the UK and beyond.