National HGTAL Core

国家HGTAL核心

• 批准号: 7144459
• 负责人: DAVID M KRISKY
• 金额: $ 91.63万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144459
• 关键词: Adenoviridae; Herpesviridae; Retroviridae; adeno associated virus group; biomedical facility; biotechnology; gene therapy; genetic strain; plasmids; recombinant virus; transfection /expression vector

The Human Gene Therapy Applications Laboratory (HGTAL)-National Core will continue to serve as a national resource for all NHLBI supported investigators pursuing clinical gene therapy applications. Since its initiation, the HGTAL has produced and certified 7 retroviral producer cell Master Cell Banks (MCBs) and Clinical retroviral supernatant derived from 4 of these MCBs have been used in Phase 1 and 2 clinical trials. For Adenoviral vectors, the HGTAL-National Core has produced and certified a MCB and a Master Working Cell Bank (MWCB) of HEK-293 cells, produced two different Adenoviral vector MVBs and produced an Ad.iNOS Final Product (FP). Also, the core has produced and certified a MCB of HSV trans-complementation cells, two different HSV Master Viral Banks (MVBs) and is currently producing HSV vector FP. Moreover, the methods for clinical production and purification of clinical grade AAV serotypes 6 and subsequently 8 are being developed by the HGTAL that will allow production of AAV FP within the first year. The facility will be able to produce up to three of each type of vector per year. Thus the primary function of the HGTAL-National Core will remain the production of clinical grade recombinant Viral Vector Final Products (FP) for all eligible NHLBI supported investigators pursuing gene therapy clinical trials. The HGTAL-National Core is able to produce for NHLBI supported investigators, as needed, clinical grade Retoviral, Herpes Simplex and Adenoviral Vectors and within the next year will be able to produce adeno-associated virus (AAV) serotypes 6 and 8. It anticipated that the Core will be able to produce up to three of each type of vector per year. The HGTAL also is able to manufacture and certify all necessary clinical intermediate products such as Master Cell Banks (MCB), Master Viral Banks, and plasmid stocks needed to produce clinical grade viral vector FP and has developed scalable methods of vector production that can be used to produce these materials under compliance with the cGMP directives of the 21Code of Federal Regulations (21CFR). The Core also has developed validated lot release assays, as required by the FDA, for clinical grade recombinant Retroviral, Adenoviral, and Herpes viral Final Products and is developing lot release assays for Adeno-Associated Virus serotypes 6 and subsequently 8 final products. Finally, the Core is able to assist investigators in preparing regulatory submissions of their studies to include IBC, RAC, FDA, and their IRB.

人类基因治疗应用实验室（HGTAL）-国家核心将继续作为所有NHLBI支持的研究人员追求临床基因治疗应用的国家资源。自成立以来，HGTAL已生产并认证了7个逆转录病毒生产细胞主细胞库（MCB），其中4个MCB的临床逆转录病毒上清液已用于I期和II期临床试验。对于腺病毒载体，HGTAL国家核心已经生产并认证了HEK-293细胞的MCB和主工作细胞库（MWCB），生产了两种不同的腺病毒载体MVB，并生产了Ad.iNOS最终产品（FP）。此外，该中心还生产并认证了一种HSV反式互补细胞MCB，两种不同的HSV主病毒库（MVB），目前正在生产HSV载体FP。此外，HGTAL正在开发临床级AAV血清型6和随后的8的临床生产和纯化方法，这将允许在第一年内生产AAV FP。该设施每年每种病媒最多可生产三种。因此，HGTAL-国家核心的主要功能将仍然是为所有符合条件的NHLBI支持的进行基因治疗临床试验的研究者生产临床级重组病毒载体最终产品（FP）。HGTAL-国家核心能够为NHLBI支持的研究人员生产临床级逆转录病毒，单纯疱疹病毒和腺病毒载体，并在明年内能够生产腺相关病毒（AAV） 血清型6和8。它预计，核心每年将能够生产每种类型的载体多达三个。HGTAL还能够生产和认证所有必要的临床中间产品，如生产临床级病毒载体FP所需的主细胞库（MCB）、主病毒库和质粒储备液，并开发了可用于生产符合cGMP的这些材料的可扩展载体生产方法 联邦法规第21条（21 CFR）的指令。根据FDA的要求，Core还开发了临床级重组逆转录病毒、腺病毒和疱疹病毒最终产品的经验证批放行检测试剂盒，并正在开发腺相关病毒血清型6和随后的8最终产品的批放行检测试剂盒。最后，核心能够帮助研究者准备其研究的监管提交文件，包括IBC、RAC、FDA和 他们的IRB。