Scientific Core One

科学核心一

• 批准号: 10589643
• 负责人: Corey Casper
• 金额: $ 37.52万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-30 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589643
• 关键词: Antigen Targeting; Antigens; Binding; Biological; Cells; Clinical; Cloning; Complement 4b; Complex; DNA; Data; Evaluation; Flow Cytometry; Formulation; Fred Hutchinson Cancer Research Center; Future; Genetic Transcription; HIV; Harvest; In Vitro; Liquid substance; Membrane; Molecular Sieve Chromatography; Nanostructures; Phase I Clinical Trials; Process; Production; Protocols documentation; RNA; RNA amplification; RNA delivery; RNA replication; RNA vaccine; Research; Ribonucleases; Techniques; Technology; Testing; Transfection; Vaccine Production; Vaccines; Venezuelan Equine Encephalitis Virus; Western Blotting; biophysical properties; delivery vehicle; design; immunogenicity; in vivo evaluation; manufacture; nanoparticle; nanoparticle delivery; particle; plasmid DNA; product development; research and development; stability testing; structured lipid; vaccine evaluation; vaccine platform

Abstract Scientific Core One has the responsibility of creating, validating, and providing R&D-grade HIV-Env immunogen-expressing self-amplifying RNAs (saRNAs) complexed with the nanostructured lipid carrier (NLC) delivery vehicle to project leads at Fred Hutchinson Cancer Research Center for in vivo testing as described in Scientific Project One. AAHI’s saRNA/NLC vaccine platform has previously demonstrated robust immunogenicity against many antigen targets, including HIV, and unparalleled stability. This technology will now be adapted to deliver the HIV immunogens of our partners at the Fred Hutchinson Cancer Research Center. Scientific Core One activities include design and cloning of the saRNA template DNA plasmids, saRNA production using well-characterized and validated in vitro transcription and purification processes, and manufacturing of the NLC delivery formulation. Upon successful saRNA and NLC manufacture, Scientific Core One will complex of saRNA/NLC vaccine and test these vaccines in vitro to verify successful saRNA replication and antigen production. Scientific Core One will also provide transfected cell materials to Scientific Core Two for immunogen antigenicity testing. Finally, the stability of these R&D-grade saRNA, NLC, and complexed saRNA/NLC materials will be verified using standard stability testing techniques to gather necessary data to enable GMP manufacturing by Scientific Project Two, successful filing of an IND and completion of a Phase I clinical trial.

摘要 Science Core One负责创建、验证和提供研发级艾滋病毒环境 免疫基因表达自扩增核糖核酸(SarNas)与纳米脂质载体(NLC)的复合 将车辆运送到弗雷德·哈钦森癌症研究中心的项目线索，以进行体内测试，如 科学计划一号。AAHI的SARNA/NLC疫苗平台之前表现出了强大的生命力 对包括艾滋病毒在内的许多抗原靶标具有免疫原性和无与伦比的稳定性。这项技术将 现在被改装为提供我们在弗雷德·哈钦森癌症研究中心的合作伙伴的艾滋病毒免疫原 中心。科学核心一活动包括设计和克隆SARNA模板DNA质粒 使用经过良好表征和验证的体外转录和纯化过程进行生产，以及 制造NLC递送配方。在成功制造Sarna和NLC后，Science Core 人们将合成Sarna/NLC疫苗，并在体外测试这些疫苗，以验证是否成功复制了Sarna 和抗原的产生。科学核心一号还将向科学核心二号提供转基因细胞材料 用于免疫原抗原性测试。最后，对这些研发级SARNA、NLC和复合体的稳定性进行了考察 SARNA/NLC材料将使用标准稳定性测试技术进行验证，以收集必要的数据 通过科学项目二、成功提交IND和完成第一阶段实现GMP生产 临床试验。