Packaging Cell Lines for Lentiviral Vector Products

慢病毒载体产品的包装细胞系

基本信息

批准号：
7909260
负责人：
KENNETH CORNETTA
金额：
$ 19.89万
依托单位：
RIMEDION, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-10 至 2011-09-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7909260
关键词：
Acquired Immunodeficiency Syndrome Agreement Alphavirus Antibodies Biological Biological Products Biotechnology CD4 Positive T Lymphocytes Cell Line Cells Certification Clinical Clinical Trials Communicable Diseases Dental Development Disadvantaged Disease Engineered Gene Family Felidae Future Generations Genes Genetic Engineering Glycoproteins Goals Green Fluorescent Proteins HIV-1 Heart Diseases Hematopoietic stem cells Hereditary Disease Indiana Lentivirus Vector Licensing Licensure Malignant Neoplasms Mediating Medical Methodology Methods Mission NIH Program Announcements Nucleic Acid Vaccines Orphan Drugs Phase Phase I Clinical Trials Production Proteins Protocols documentation Research Research Personnel Retroviridae Rivers Ross river virus Scheme Series Small Business Technology Transfer Research Technology Testing Transfection Transgenes United States National Institutes of Health Universities Vesicular stomatitis Indiana virus Viral Virus adenosine deaminase adenosine deaminase deficiency base cancer genetics cell type commercialization design gene therapy glycoprotein G in vivo large scale production manufacturing process medical schools meetings novel particle pre-clinical programs public health relevance vector

项目摘要

DESCRIPTION (provided by applicant): HIV-1 based lentiviral vectors are becoming an increasingly attractive means of integrating transgenes into target cells. Vectors are in or enterning clinical trials for a diverse group of ailments, including genetic disease, AIDS and cancer. To expand the range of target cells beyond that of HIV-1 (CD4+ cells), vectors are pseudotyped with various viral envelopes. Rimedion has identified the Ross River Virus (RRV) and the feline RD114 envelope glycoproteins to be promising candidates for production of stable packaging cell lines. In this STTR application, Rimedion and its research partner, Indiana University School of Medicine proposes to develop novel, stable lentiviral packaging cell lines using these envelope. These lines will be useful for further preclinical development and will also be suitable for future clinical use. Specific Aim 1: Rimedion will generate stable packaging lines expressing the RRV and RD114 envelopes. Specific Aim 2: Using the packaging cell lines for RRV and RD114, generate stable lentiviral producer cell lines expressing the Green Fluorescent Protein to be used for studies of vector titer, long-term cell line stability and replication competent lentiviral testing. These cell lines will replace the current manufacutring methodolgy (transient transfection) for lentiviral vectors which is not suitable for large scale productions and limits the potential of lentiviral vectors from achieving licensure by the FDA. If successful, these cell lines will provide the platform technology for a large group of new biologic agents. Phase II will include the certification to meet FDA Guidances so the lines may be used in Good Manufacturing Practices. As part of Phase II, the RD114 cell line would be used to create a producer cell line for treatment of adenosine deaminase deficieny in a Phase I clinical trial. Through appropriate material agreements, the lines will also be made available to academic investigators for investigational, non-commerical use through NIH sponsored programs such as the National Gene Vector Biorepostory. PUBLIC HEALTH RELEVANCE: Gene therapy mediated by lentiviral vectors is now in clinical trials and holds promise for a wide variety of genetic diseases, AIDS and cancer. A major limitation to commercialization of these biologic products is large- scale production technology. Rimedion proposes to generate a series of lentiviral packaging cell lines that will allow manufacturing of lentiviral products suitable for FDA licensure specifications.

描述（由申请人提供）：基于 HIV-1 的慢病毒载体正在成为将转基因整合到靶细胞中的越来越有吸引力的手段。载体正在或正在进入针对多种疾病的临床试验，包括遗传病、艾滋病和癌症。为了将靶细胞范围扩大到 HIV-1（CD4+ 细胞）之外，载体采用各种病毒包膜进行假型化。 Rimedion 已确定罗斯河病毒 (RRV) 和猫科动物 RD114 包膜糖蛋白是生产稳定包装细胞系的有希望的候选者。在此 STTR 申请中，Rimedion 及其研究合作伙伴印第安纳大学医学院提议使用这些包膜开发新型、稳定的慢病毒包装细胞系。这些细胞系将有助于进一步的临床前开发，也适用于未来的临床使用。具体目标 1：Rimedion 将生成表达 RRV 和 RD114 信封的稳定包装线。具体目标 2：使用 RRV 和 RD114 的包装细胞系，生成表达绿色荧光蛋白的稳定慢病毒生产细胞系，用于载体滴度、长期细胞系稳定性和复制能力慢病毒测试的研究。这些细胞系将取代目前慢病毒载体的制造方法（瞬时转染），该方法不适合大规模生产，并限制了慢病毒载体获得 FDA 许可的潜力。如果成功，这些细胞系将为一大群新生物制剂提供平台技术。第二阶段将包括满足 FDA 指南的认证，以便这些生产线可以用于良好生产规范。作为 II 期的一部分，RD114 细胞系将用于创建生产细胞系，用于在 I 期临床试验中治疗腺苷脱氨酶缺乏症。通过适当的材料协议，这些细胞系还将通过国家卫生研究院资助的项目（例如国家基因载体生物储存库）提供给学术研究人员用于研究、非商业用途。公共健康相关性：由慢病毒载体介导的基因治疗目前正在进行临床试验，有望治疗多种遗传疾病、艾滋病和癌症。这些生物产品商业化的主要限制是大规模生产技术。 Rimedion 计划生成一系列慢病毒包装细胞系，以生产符合 FDA 许可规范的慢病毒产品。