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

使用新型核酸递送平台开发用于通用流感治疗和预防的生物抗病毒药物的临床前开发

• 批准号: 10456296
• 负责人: Lyndsey Linke
• 金额: $ 100.01万
• 依托单位: SIVEC BIOTECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-20 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456296
• 关键词: Adult; Advanced Development; Amino Acids; Animals; Antibiotics; Antiviral Agents; Antiviral Therapy; Antiviral resistance; Avian Influenza; Avidity; Bacteria; Binding; Biodistribution; Biological; Biomedical Engineering; Biotechnology; Cell Death; Cells; Clinical; Collaborations; Complement; Development; Disease Outbreaks; Domestic Fowls; Economic Burden; Engineering; Epithelial; Epithelial Cells; Evaluation; Ferrets; Flu virus; Formulation; Foundations; Freeze Drying; Gene Expression; Genes; Genomics; Goals; Health; Hepatotoxicity; Human; In Vitro; Incidence; Industry; Infection; Infectious Disease Epidemiology; Influenza; Inhalation; Invaded; Laboratories; Lung; Measures; Medical; Modeling; Morbidity - disease rate; Mucous Membrane; Mus; Nebulizer; Nose; Nucleic Acids; Parents; Particle Size; Patients; Persons; Phase; Physiology; Plasmids; Population; Positioning Attribute; Preventive treatment; Process; Prophylactic treatment; Proteins; Public Health; RNA Interference; RNA Interference Pathway; Readiness; Regulatory Pathway; Research; Respiratory Mucosa; Risk; Safety; Seasons; Specificity; Structure of parenchyma of lung; System; Technology; Testing; Therapeutic; Therapeutic Effect; Tissues; Transcript; Translations; Vaccination; Vaccines; Viral; Viral Vector; Virus Replication; Work; analytical method; auxotrophy; base; clinical application; clinical practice; clinically relevant; commercialization; cost; cytotoxicity; delivery vehicle; drug efficacy; experience; flu; high risk population; human model; immunogenicity; in vivo; influenza infection; influenza virus vaccine; influenzavirus; interest; knock-down; method development; mortality; mouse model; multimodality; novel; novel strategies; novel therapeutic intervention; nucleic acid delivery; nucleic acid-based therapeutics; pandemic disease; pandemic influenza; pathogen; phase 1 study; phase 2 study; pre-clinical; preclinical development; preclinical study; preservation; prevent; product development; programs; respiratory; seasonal influenza; sialic acid receptor; small hairpin RNA; success; tumorigenesis; uptake; vaccine efficacy; viral RNA; viral resistance

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.

该项目的目标是推进一种针对人类的新型生物抗病毒药物（SiVEC-IAV™）的开发