Targeting lentiviruses to infect chosen cells

靶向慢病毒感染选定的细胞

• 批准号: 7171541
• 负责人: Pin Wang
• 金额: $ 56.89万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171541
• 关键词: Address; Alphavirus; Animal Model; Antibodies; Antibody Repertoire; Antigens; Aura virus; Baltimore; Binding; Biomedical Engineering; CD20 Antigens; CD34 gene; Cells; Chemokine (C-C Motif) Receptor 5; Chimeric Proteins; Collaborations; Cytoplasmic Tail; Cytosol; DNA; Data; Dendritic Cells; Dengue Virus; Disease; Endocytosis; Endosomes; Engineering; Environment; Epitopes; Flavivirus; Gene Delivery; Generations; Glycoproteins; Goals; HIV; Hematopoietic stem cells; Human; Immunology; In Situ; In Vitro; Inborn Errors of Metabolism; Individual; Infection; Intention; Intravenous; Laboratories; Lead; Lentivirus Vector; Light; MS4A1 gene; Malignant Neoplasms; Mammalian Cell; Mediating; Membrane; Membrane Fusion; Methods; Molecular; Monitor; Mus; Organ; Polymerase Chain Reaction; Preparation; Process; Production; Proteins; Proto-Oncogene Protein c-kit; Range; Recombinants; Research Personnel; Ross river virus; Semliki forest virus; Small Interfering RNA; Stem Cell Factor; Structure; Study Section; Subfamily lentivirinae; Surface; System; Therapeutic; Tick-Borne Encephalitis Virus; Tick-Borne Encephalitis Viruses; Tissues; Vaccination; Viral; Virion; Virus; Virus Diseases; Work; cancer therapy; cell type; design; gene delivery system; gene therapy; improved; in vivo; melanoma; molecular modeling; neoplastic cell; novel; novel strategies; programs; receptor; receptor binding; recombinant virus; research study; tool; tositumomab; vector; virology; vpr Gene Products

DESCRIPTION (provided by applicant): Gene therapy is amenable for correcting inborn errors of metabolism, as well as for the treatment of cancer and HIV. Lentiviral vectors are among the most efficient tools for gene delivery into mammalian cells. Our long-term goal is to develop a targetable gene delivery system that can transduce a specific cell type, a specific tissue or a specific organ after intravenous adminstration. Our preliminary studies have uncovered a truly targetable lentiviral vector system for gene delivery. The experimental focus of this proposal is to evaluate the therapeutic potential of this method for in vivo targeting. The first specific aim is to study the molecular mechanism of targeted infection by engineered recombinant viruses. Understanding this process should lead to identification and design of new molecules for targeting. The second specific aim is to perfect the strategy to prepare lentiviruses, which will greatly enhance the efficacy of virus preparation. The third specific aim is to explore novel molecules for targeting lentiviral vectors, which will expand our ability to manipulate lentiviruses for targeting. The fourth specific aim is to explore the utility of targeted gene delivery using antibody- and SCF-bearing lentiviruses. These studies build upon our novel finding that viruses displaying membrane-bound antibodies or stem cell factor (SCF) can specifically infect cells expressing cognate antigens or SCF receptors. Various experiments are proposed to assess the therapeutic implications of this novel targeting strategy to treat HIV and cancer in animal models. Taken together, these novel studies will enlarge the therapeutic potential of targeted gene delivery to treat a diverse range of diseases, as well as advance our undstanding of viral infection.

描述（由申请人提供）：基因治疗可用于纠正代谢的先天错误以及癌症和HIV的治疗。慢病毒载体是将基因递送到哺乳动物细胞中的最有效的工具之一。我们的长期目标是开发一个可靶向的基因递送系统，该系统可以在静脉内施用后转导特定的细胞类型，特定的组织或特定器官。我们的初步研究已经发现了一个真正可靶向的慢病毒载体系统，用于基因输送。该建议的实验重点是评估该方法在体内靶向的方法。第一个具体目的是研究通过工程重组病毒靶向感染的分子机制。了解此过程应导致鉴定和设计用于靶向的新分子。第二个具体目的是完善制备慢病毒的策略，这将大大提高病毒制备的功效。第三个具体目的是探索靶向慢病毒载体的新分子，这将扩大我们操纵慢病毒靶向的能力。第四个特定目的是使用抗体和含有SCF的慢病毒探索靶向基因递送的实用性。这些研究基于我们的新发现，即表现出膜结合的抗体或干细胞因子（SCF）可以特异性地感染表达同源抗原或SCF受体的细胞。提出了各种实验来评估这种新颖的靶向策略在动物模型中治疗艾滋病毒和癌症的治疗意义。综上所述，这些新的研究将扩大靶向基因递送的治疗潜力，以治疗多种疾病，并推动我们对病毒感染的不可思议。