DNA to RNA: An Inclusive Canadian Approach to Genomic-based RNA Therapeutics (D2R)

基因组学与RNA技术相结合的力量体现在针对SARS-CoV-2的信使核糖核酸疫苗的显著和迅速的成功。我们正处于一场革命的开端，这场革命将使基于基因组引导的RNA药物的快速、低成本开发成为可能，用于治疗一系列疾病，例如由新兴病毒引起的疾病，这些病毒以大流行及其相关的灾难性健康和经济后果威胁我们的社会，高负担疾病，如癌症，是加拿大的头号死因，以及罕见的无法治愈或治疗昂贵的罕见遗传疾病。D2R计划基于麦吉尔大学、麦克马斯特大学、舍布鲁克大学、渥太华大学和不列颠哥伦比亚大学的研究人员的力量和卓越。D2R基于一种多学科工作包方法，以指导基于RNA的药物的开发，以沉默或编辑基因，取代有缺陷的蛋白质，并改进基于细胞的治疗。包括大数据技术、分析和人工智能在内的新型计算和统计方法将通过支持对大数据集和药物设计的分析和解释来实现这些进步。一个强大的临床和制药/生物技术行业合作网络将开展概念验证临床试验和其他活动，以加快商业化和临床转化。基于它们给人类健康和经济带来的巨大负担，以及它们对RNA疗法设计的适应性，我们首先将重点放在三个疾病领域：病毒感染、精确肿瘤学和罕见的遗传疾病。经济影响将来自于在加拿大建立一个基于RNA的药物开发的纽带，作为与制药和生物技术合作的枢纽，以加快向监管批准的进展。为了成功实施和部署这些药物，特别是针对服务不足和寻求公平的人群，包括加拿大的土著社区，以及在老年人等弱势群体中，我们将创建和分析各种社会基因组数据集，并调查和解决伦理、法律和社会问题，如公众认知、歧视和公平获得机会。这些机制将通过与患者协会、土著社区和其他寻求公平的团体的接触和协商，为加拿大人提供发言权，并向政府提供政策建议。

The power of combining genomics with RNA technology is exemplified by the remarkable and rapid success of mRNA vaccines against SARS-CoV-2. We are at the beginning of a revolution that will enable the rapid, low-cost development of genome-guided RNA-based medicines for a wide spectrum of diseases, such as those caused by emerging viruses that threaten our society with pandemics and their associated catastrophic health and economic consequences, high-burden diseases such as cancer, which is the number one cause of death in Canada, and rare genetic disorders that are incurable or prohibitively expensive to treat.The D2R program is anchored in the strength and excellence of researchers at McGill University, McMaster University, Université de Sherbrooke, University of Ottawa, and University of British Columbia. D2R is based on a multi-disciplinary work package approach to guide the development of RNA-based drugs to silence or edit genes, replace defective proteins, and improve cell-based therapeutics. Novel computational and statistical methods, including big data technologies, analytics, and AI, will enable these advances by supporting the analysis and interpretation of large datasets and drug design. A strong network of clinical and pharmaceutical/biotechnology industry collaborations will conduct proof-of-concept clinical trials and other activities to accelerate commercialization and clinical translation. Based on the immense burden they place on human health and the economy, and on their amenability to the design of RNA therapeutics, we will focus initially on three disease areas: viral infections, precision oncology and rare genetic disorders. Economic impact will stem from the creation of a nexus for RNA-based drug development in Canada as a hub for partnerships with pharma and biotech to accelerate progression towards regulatory approval. To successfully implement and deploy these medicines, particularly for underserved and equity-seeking populations, including Canada's Indigenous communities, and within vulnerable groups such as the elderly, we will create and analyze diverse socio-genomic datasets and investigate and address ethical, legal and societal issues such as public perception, discrimination and equitable access. These mechanisms will provide a voice for Canadians through engagement and consultation with patient associations, Indigenous communities, and other equity-seeking groups, as well as provide policy recommendations to government.