MGH2 and Amplicon Viral Core

MGH2 和扩增子病毒核心

• 批准号: 7597043
• 负责人: DAVID M KRISKY
• 金额: $ 22.63万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7597043
• 关键词: Area; Attenuated; Cells; Clinical; Clinical Data; Clinical Research; DNA; DNA Viruses; Generations; Goals; Herpesvirus 1; Proteins; Protocols documentation; Quality Control; Research Personnel; Viral; Virus; mutant; particle; pre-clinical; preclinical study; programs; vector

The clinical study of neuro-attenuated replication competent HSV-1 mutants deleted for gamma-34.5 and ICP6 and amplicon vectors has been limited by the inability to consistently produce vector stocks in adequate quantity and quality. The goal of Core B will be to provide program investigators with MGH2 (gamma-34.5/ICP6 mutant) and amplicon viral stocks that are both high in titer and highly purified while Deing consistently produced according to vector specific protocols. Vector stocks produced in this manner will be characterized across all major quality control areas that make up lot release criteria of DNA viruses for clinical use. This approach will result in generation of pre-clinical data that will not be hampered by issues of bio-equivalency between vector stocks that are used for pre-clinical studies and those that may be used later in a clinical setting. The use of highly purified and characterized vector stocks will also allow program investigators to more completely understand the potential efficacy and mechanism of activity of vector delivery in the pre-clinical setting without the worry of spurious results that may result from the use of nonuniform vector stocks or vector stocks that are contaminated with wild type virus or high levels of defective particles, contaminating proteins, or host cell DNA.

缺失γ-34.5和神经减弱复制能力的HSV-1突变体的临床研究 ICP6 和扩增子载体因无法持续生产载体库存而受到限制 足够的数量和质量。 Core B 的目标是为项目研究人员提供 MGH2 （gamma-34.5/ICP6 突变体）和扩增子病毒储液，滴度高且纯度高，同时 Deing 始终根据载体特定协议生产。以这种方式产生的载体库存 将在构成 DNA 病毒批次放行标准的所有主要质量控制领域进行表征 供临床使用。这种方法将产生不受问题阻碍的临床前数据 用于临床前研究的载体库存与可能使用的载体库存之间的生物等效性 后来在临床环境中。使用高度纯化和特征化的载体库存也将允许程序 研究人员更全面地了解载体的潜在功效和活性机制 在临床前环境中进行交付，无需担心因使用不均匀的试剂可能导致的虚假结果 载体库存或被野生型病毒污染或高水平缺陷病毒的载体库存 颗粒、污染蛋白质或宿主细胞 DNA。