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

核酸疗法（NATs）通过以靶向的方式解决罕见病的遗传原因，为治疗罕见病提供了巨大的潜力。在过去几年中，NAT临床试验的指数级增长清楚地证明了这些分子在转化研究中的作用，以及研究者主导的临床前和临床研究的独特机会，英国在这方面具有特殊的记录优势。为了进一步促进英国RD患者核酸治疗的发展，我们正在创建一个名为“建立英国罕见病核酸治疗发展平台”（UPNAT）的节点。UPNAT将把包括科学家、临床医生、遗传学家、受训者、患者倡导团体和慈善机构、工业伙伴、国际非营利组织和监管机构在内的相关利益攸关方聚集在一起，建立和协调一个国家网络，以促进利用快速发展的NATs。UPNAT打算解决目前在英国研发领域NAT研究和开发遇到的一些挑战，包括1)缺乏跨学科知识交流和领导NAT临床前和临床开发中心之间专业知识共享的国家基础设施；2)明确的途径，系统地将携带独特突变的患者与NAT专家联系起来；3)监管机构和研究人员之间需要持续对话，以简化监管审批过程，监测结果，加速研发特异性NATs的临床转化。为了应对这些挑战，UPNAT将创造以下交流机会：1)科学研讨会，促进研究人员、临床和行业利益相关者之间的跨学科知识交流；2)患者权益团体、慈善机构和研究人员之间的网络研讨会和活动，以促进公众参与；3)培训计划，教育和装备下一代科学家和临床医生的知识和技能，以领导未来的NAT研究项目。该节点包括三个互补的项目，以解决总体目标和关键瓶颈。这些项目的重点是1)靶点选择、NAT策略设计和临床前开发；2)提高英国在为研发量身定制的NAT规模化合成和中试毒理学研究方面的能力；3) NAT临床试验设计及监管审批。总的来说，这些工作包将为英国研发中心采用的NAT的设计、开发和临床翻译提供一个强大的框架。UPNAT将专注于罕见儿科和成人疾病的独特优势领域，包括由伦敦、牛津、剑桥、伯明翰、利物浦和谢菲尔德的合作组织以及伦敦大学学院眼科研究所、神经病学研究所、摩尔菲尔德眼科医院和大学学院医院的成人专家中心提供的六项儿科高度专业化服务。该节点将专注于神经、神经退行性、代谢和眼科疾病，这些疾病特别有利于NAT的应用，随着NAT技术的快速进步和node的发展，该节点将继续向其他疾病领域开放。UPNAT将由来自伦敦大学学院大奥蒙德街儿童健康研究所、眼科研究所、神经病学研究所、大奥蒙德街医院（GOSH）、摩尔菲尔德眼科医院、UKRI NATA（牛津）的研究人员和合作者以及来自牛津、剑桥和伯明翰的研究人员领导。Node的成员将与英国基因组学公司、英国国立卫生研究院的五个brc （GOSH、UCLH、Moorfields、Oxford和Cambridge）、行业、患者倡导团体和慈善机构、英国监管机构以及研发领域的NAT国际联盟合作。总的来说，我们装备齐全，并决心最大限度地发挥NAT为英国内外的研发患者社区提供的变革潜力。

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.