Development of a Safe and Effective COVID-19 Vaccine and Booster Using Linear Covalently Closed DNA Minivectors

COVID-19大流行无论在全球传播还是经济影响方面，都不同于世界上世纪以来的任何一次。 除了非药物干预措施外，迫切需要疫苗和疗法来有效根除COVID-19。Mediphage Bioceuticals位于安大略省基奇纳，是一家遗传医学公司，开发遗传性眼部疾病的治疗方法，并有可能扩展到更广泛的治疗领域。他们的旗舰技术ministringDNA（msDNA）是一种安全有效的基因递送载体，可用于治疗选择有限或没有治疗选择的遗传疾病。 该项目的目标是与兰顿学院合作，使用MBI的线性共价闭合（LCC）DNA微载体生产安全有效的疫苗和加强剂。MBI和兰顿学院之前的合作已经成功优化了MBI开发的用于生产LCC msDNA的发酵和小规模纯化工艺。迄今为止，LCC DNA与其他DNA种类的分离，无论是通过大小和拓扑结构，尚未实现超出分析水平的纯化。产生商业上可行的疫苗需要产生大规模msDNA生产的有效且按比例放大的方法。 该项目的成功完成将使Mediphage能够生产进行体外和体内模型临床前有效性测试所需的msDNA-VLP体积。这项研究的成功将对加拿大人的未来产生巨大影响，因为疫苗是结束COVID-19全球大流行并让加拿大和全球经济开始复苏所必需的。

The COVID-19 pandemic is unlike anything the world has seen in over a century, both in terms of global spread and economic impact. In addition to non pharmaceutical interventions, there is an urgent need for vaccines and therapies to effectively eradicate COVID-19. Mediphage Bioceuticals located in Kitchener, ON is a genetic medicine company developing therapeutics for inherited ocular diseases, with the potential to expand to broader therapeutic areas. Their flagship technology, ministring DNA (msDNA), is a safe and effective gene delivery vector that can be used to cure genetic diseases that have limited, or no treatment options available. The objective of this proposed project in collaboration with Lambton College is to produce a safe and effective vaccine and booster using MBI's linear covalently closed (LCC) DNA minivectors. MBI and Lambton College's previous collaborations have resulted in the successful optimization of the fermentation and small scale purification processes developed by MBI for the production of LCC msDNA. To date, separation of LCC DNA from other DNA species, both by size and topology has yet to be achieved beyond analytical levels of purification. An efficient and scaled-up approach to generate large scale msDNA production is required for generation of a commercially viable vaccine. Successful completion of this project will allow Mediphage to produce the volume of msDNA-VLP necessary to conduct preclinical efficacy testing of in vitro and in vivo models. The success of this study will have colossal impacts for the future of Canadians as a vaccine is necessary to end the COVID-19 global pandemic and allow the Canadian and global economy to begin recovering.