Preclinical development of a biological antiviral for universal influenza treatment and prophylaxis using a novel nucleic acid delivery platform

该项目的目标是促进开发一种新的生物抗病毒药物（SiVEC-IAV™）， 流感。流感是一个全球性的公共卫生问题，感染了大约20%的美国人口 每年都有超过110亿美元的经济负担。虽然目前可用 流感疫苗和抗病毒药物是预防和治疗流感的实用方法， 现有的产品是次优的，并且它们对许多患者是禁忌的。为了满足新的需求， 为了预防和管理流感，SiVEC生物技术公司开发了一种新的生物抗病毒药。我们 核心使能技术是一种通用的核酸递送平台，其特征在于非免疫原性， 非致病性细菌为了用作流感病毒抗病毒剂（SiVEC-IAV），细菌被编程为 组成型表达短发夹RNA（shRNA）分子，并将其直接靶向递送至粘膜 上皮细胞，其中RNA干扰（RNAi）途径降解病毒转录物，所述转录物是 流感感染。I期研究证明了SiVEC-IAV的安全性、有效性和商业潜力。 II期研究将通过IND指导和临床前研究推进SiVEC-IAV，包括优化 SiVEC-IAV运载工具（目标1）; SiVEC-IAV制剂和初步产品的定义 本发明的目的在于提供一种用于评价SiVEC-IAV在人流感的雪貂模型中的作用的方法（目的2）;以及评价SiVEC-IAV在人流感的雪貂模型中的作用（目的3）。长期 目标是获得FDA批准SiVEC-IAV，使其广泛使用成为可能。我们希望SiVEC-IAV， 结合每年的疫苗接种和其他预防和治疗措施， 多模式的方法，以减少流感的发病率以及成本负担。这种独特的方法， 安全地将核酸递送到适当的细胞和组织以促进治疗效果 与将基于RNAi的疗法转化为临床实践相关的多种障碍。此外该 SiVEC递送平台可以定制以递送其他核酸和基因编辑系统到临床应用。 相关组织，以将其效用扩展到基于RNAi的治疗领域之外。

The goal of this project is to advance the development of a novel biologic antiviral (SiVEC-IAV™) against human influenza. Influenza is a worldwide public health problem that infects approximately 20% of the U.S. population annually and is associated with an annual economic burden of over $11 billion USD. Although currently available influenza vaccines and antivirals are practical approaches to prevent and treat influenza, the efficacy of all available products is suboptimal and they are contraindicated for many patients. To meet the need for new approaches to prevent and manage influenza, SiVEC Biotechnologies developed a novel biological antiviral. Our core-enabling technology is a versatile nucleic acid delivery platform that is characterized as non-immunogenic, non-pathogenic bacteria. For use as an influenza antiviral (SiVEC-IAV) the bacteria are programmed to constitutively express short hairpin RNA (shRNA) molecules, and target their delivery directly to mucosal epithelial cells, where the RNA interference (RNAi) pathway degrades viral transcripts that are necessary for influenza infection. Phase I studies demonstrated the safety, efficacy, and commercial potential of SiVEC-IAV. Phase II studies will advance SiVEC-IAV through IND-directed and preclinical studies, including optimization of the SiVEC-IAV delivery vehicle (Aim 1); definition of the SiVEC-IAV formulation and preliminary product specifications (Aim 2); and evaluation of SiVEC-IAV in a ferret model of human influenza (Aim 3). The long-term goal is to obtain FDA approval of SiVEC-IAV and make its widespread use possible. We expect that SiVEC-IAV, in combination with annual vaccination and other preventative and treatment measures, will be part of a multimodal approach to reduce the incidence of influenza as well as the cost burden. This unique approach to safely delivering nucleic acids to the appropriate cells and tissues to facilitate a therapeutic effect overcomes multiple barriers associated with the translation of RNAi-based therapeutics into clinical practice. In addition, the SiVEC delivery platform can be tailored to deliver other nucleic acids and gene editing systems to clinically relevant tissues to extend its utility outside the realm of RNAi-based therapeutics.