Development of a Therapeutic mRNA Vaccine for COVID-19 using pHion's Delivery Technology

随着SARS-CoV-2感染的持续上升，以及相关的医疗保健和经济影响，人们竞相开发疫苗来预防这种疾病。RNA疫苗被设计为编码疾病抗原的基因序列，在这种情况下是SARS-CoV-2，并引起适当的免疫应答。有几种针对SARS-CoV-2的管道mRNA疫苗被设计用于引起预防性反应，但迄今为止还没有开发中的治疗性疫苗。为了使疫苗具有治疗性，需要一种特定类型的免疫力，称为CD 8+反应。Phion Therapeutics（贝尔法斯特SME）有一种技术，当添加到mRNA中时，可以产生产生CD 8+反应的疫苗。我们得到这种反应是因为我们可以使用细胞穿透肽（RALA）作为递送载体将疫苗递送到正确的细胞（抗原呈递细胞）中，该递送载体不被识别为外来的并且绕过先天反应。RALA被设计为当pH降低时穿过细胞膜并与内体膜融合，这促进mRNA抗原释放到胞质溶胶中而没有任何相关的毒性。我们是唯一一家拥有这种肽来运送疫苗的公司。疫苗本身是一种遗传货物（mRNA），旨在编码特定疾病中的抗原，在这种情况下，来自SARS-CoV-2的多种免疫原性蛋白。RALA擅长将所有三种mRNA浓缩成纳米颗粒，这些纳米颗粒在室温下冻干并具有独特的稳定性，而不会失去功能。研究旨在创建RALA/mRNA疫苗，验证表达ACE-2受体的人源化小鼠的基线特征，然后通过SARS-CoV-2的外包攻击研究确定仓鼠和雪貂的反应。最后，我们将制定一个监管框架，以确保进展到诊所。该项目的输出旨在使用体内模型提供可靠的预防和治疗反应的明确证据。有了一个全面的数据包，到这个18个月的项目结束时，我们将有候选疫苗进行毒理学研究。我们相信，RALA/mRNA技术标志着新一代治疗性疫苗的出现，可以在全球范围内清除病毒感染。最重要的是，这种治疗性疫苗接种的平台技术将随时提供给英国的其他行业和学术界。通过流程创新中心对自动化可扩展性的验证，pHion对供应链充满信心。

As infections with SARS-CoV-2 continue to rise with associated healthcare and economic implications, there is a race on to develop a vaccine to prevent the disease. RNA vaccines are designed to encode the genetic sequences of antigens of a disease, in this instance SARS-CoV-2 and evoke an appropriate immune response. There are several pipeline mRNA vaccines for SARS-CoV-2 that are designed to evoke a prophylactic response but as yet there is no therapeutic vaccine in development. To make a vaccine therapeutic, a particular type of immunity is required known as a CD8+ response. Phion Therapeutics (Belfast SME) have a technology that when added to mRNA, creates a vaccine that produces a CD8+ response. We get this response because we can deliver the vaccine into the correct cells (antigen presenting cells) using a cell penetrating peptide (RALA) as a delivery vehicle which is not recognised as foreign and bypasses the innate response. RALA is designed to cross cellular membranes and fuse with endosomal membranes when the pH lowers which facilitates the release of the mRNA antigens into the cytosol without any associated toxicity. We are the only company to have this peptide to deliver the vaccine. The vaccine itself is a genetic cargo (mRNA) designed to code for the antigens in a particular disease, in this instance multiple immunogenic proteins from SARS-CoV-2\. RALA is adept at condensing all three mRNA into nanoparticles which are lyophilised and uniquely stable at room temperature without losing functionality. Studies are designed to create a RALA/mRNA vaccine, validate baseline characteristics in humanised mice expressing the ACE-2 receptor, followed by determining the response in hamsters and then ferrets through outsourced challenge studies with SARS-CoV-2\. Finally, we will develop a regulatory framework to ensure progression to the clinic. Outputs from this project are designed to provide definitive evidence of a robust prophylactic and therapeutic response using in vivo models. With a comprehensive data package, by the end of this 18 month project we will have the candidate vaccine to progress to toxicology studies. We believe that the RALA/mRNA technology marks the advent of a new generation of therapeutic vaccines that could clear viral infections on a global scale. Most importantly, this platform technology for therapeutic vaccination will be made readily available to other industries and academics across the UK. With validation of automated scalability by the Centre for Process Innovation, pHion is confident of the supply chain.