Targeting lentiviruses to infect chosen cells

靶向慢病毒感染选定的细胞

基本信息

批准号：
7762182
负责人：
Pin Wang
金额：
$ 60.37万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7762182
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 Molecular Models Monitor Mus Organ Preparation Process Production Proteins Proto-Oncogene Protein c-kit 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

项目摘要

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.

基因疗法适用于纠正先天性代谢错误以及癌症的治疗慢病毒载体是将基因传递到哺乳动物细胞的最有效工具之一。我们的长期目标是开发一种可转导特定细胞类型的靶向基因传递系统，静脉给药后作用于特定组织或特定器官。我们的初步研究发现用于基因传递的真正靶向慢病毒载体系统。本提案的实验重点是评估该方法体内靶向的治疗潜力。第一个具体目标是研究工程重组病毒靶向感染的分子机制。了解这个过程应该导致识别和设计新的靶向分子。第二个具体目标是完善慢病毒的制备策略，将大大提高病毒制备的效率。第三个具体目标是探索针对慢病毒载体的新分子，这将扩展我们的能力操纵慢病毒进行靶向。第四个具体目标是探索靶向基因递送的效用使用携带抗体和 SCF 的慢病毒。这些研究建立在我们的新发现之上，即病毒展示膜结合抗体或干细胞因子（SCF）可以特异性感染表达的细胞同源抗原或 SCF 受体。提出了各种实验来评估治疗效果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意义。综合起来，这些新颖的研究将扩大靶向基因递送的治疗潜力，以治疗多种疾病疾病，并增进我们对病毒感染的了解。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Co-delivery of carboplatin and paclitaxel via cross-linked multilamellar liposomes for ovarian cancer treatment.

通过交联多层脂质体共同递送卡铂和紫杉醇用于卵巢癌治疗。

DOI：
10.1039/c7ra01100h
发表时间：
2017
期刊：
RSC advances
影响因子：
3.9
作者：
Zhang,Xiaoyang;Liu,Yarong;Kim,YuJeong;Mac,John;Zhuang,Rachel;Wang,Pin
通讯作者：
Wang,Pin

Gamma-retroviral vectors enveloped with an antibody and an engineered fusogenic protein achieved antigen-specific targeting.

DOI：
10.1002/bit.21903
发表时间：
2008-10-01
期刊：
BIOTECHNOLOGY AND BIOENGINEERING
影响因子：
3.8
作者：
Yang, Haiguang;Ziegler, Leslie;Joo, Kye-Il;Cho, Taehoon;Lei, Yuning;Wang, Pin
通讯作者：
Wang, Pin

Lentiviral vectors for immune cells targeting.