MGH2 and Amplicon Viral Core

MGH2 和扩增子病毒核心

• 批准号: 7038137
• 负责人: DAVID M KRISKY
• 金额: $ 16万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038137
• 关键词: Alphaherpesvirinae; adeno associated virus group; biomedical facility; biotechnology; gene therapy; neoplasm /cancer therapy; therapy design /development; transfection /expression 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.

HSV-1 γ-34.5和γ-34.5缺失型神经减毒复制能力突变株的临床研究 ICP6和扩增子载体的制备受到不能一致地产生载体储备物的限制， 足够的数量和质量。核心B的目标是为项目研究者提供MGH 2 （γ-34.5/ICP6突变体）和扩增子病毒原液，其滴度高且高度纯化， Deing始终根据载体特异性方案生产。以这种方式生产的载体股票 将在构成DNA病毒批放行标准的所有主要质量控制领域进行表征 供临床使用。这种方法将产生不会受到问题阻碍的临床前数据 用于临床前研究的载体储备与可能用于临床前研究的载体储备之间的生物等效性 后来在临床上。使用高度纯化和特征化的载体储备物也将允许程序化。 研究人员更全面地了解载体的潜在功效和活性机制 在临床前环境中输送，而不用担心可能由于使用不均匀的 被野生型病毒或高水平缺陷型病毒污染的病媒原种或病媒原种 颗粒、污染蛋白质或宿主细胞DNA。