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 Scientific Core One负责创建、验证和提供研发级HIV-Env 与纳米结构脂质载体（NLC）复合的免疫原表达自扩增RNA（saRNA） 递送载体至Fred哈钦森癌症研究中心的项目负责人，用于体内测试，如 科学计划一AAHI的saRNA/NLC疫苗平台此前已证明具有强大的 对许多抗原靶标，包括HIV的免疫原性和无与伦比的稳定性。这项技术将 我们的合作伙伴弗雷德哈钦森癌症研究所的HIV免疫原 中心Scientific Core One的活动包括设计和克隆saRNA模板DNA质粒、saRNA 使用充分表征和验证的体外转录和纯化方法生产，以及 NLC递送制剂的制造。在成功生产saRNA和NLC后，Scientific Core 将saRNA/NLC疫苗复合物并在体外测试这些疫苗以验证成功的saRNA复制 和抗原产生。科学核心一号还将向科学核心二号提供转染的细胞材料 用于免疫原抗原性检测。最后，这些R& D级saRNA、NLC和复合物的稳定性 将使用标准稳定性测试技术验证saRNA/NLC材料，以收集必要的数据， 通过科学项目二实现GMP生产，成功提交IND并完成I期 临床试验