课题基金 / 基金详情

EPISOMAL VECTORS FOR COLON CANCER GENE THERAPY

EPISOMAL VECTORS FOR COLON CANCER GENE THERAPY
结肠癌基因治疗的特殊载体
批准号:
6137584
负责人:
MARK J COOPER
金额:
$13.59万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-01-20 至 2000-12-31

项目摘要

项目成果

MARK J COOPER的其他基金

相似基金

相关文献

中文摘要
翻译
描述:(申请人的摘要)申请人的实验室最近 开发了一种新的基于SV 40的人基因游离型表达载体 预期安全的治疗应用,同时允许高拷贝 在人类细胞中复制。 这种游离型质粒利用一种特异性的 设计SV 40大T抗原突变体以驱动染色体外复制 同时消除了大T抗原的不期望的能力, 结合并抑制宿主p53和RB肿瘤抑制基因蛋白。 因为 该载体在基因转染后2-3天复制到数千个拷贝, 转移,预测表达系统安全地表达靶基因 每个细胞的水平高于任何目前公开的基因治疗载体。 为了进一步修改该向量,以包括适当的安全性和 复制控制元件,申请人提出开发一种新颖的 “结肠癌特异性”表达系统, 在染色体外,并且仅在肿瘤细胞中表达靶基因。 具体 目的1是开发一种非感染性的、安全性修饰的基于SV 40的游离型 允许肿瘤特异性载体的外部控制的表达系统 扩增和基因表达。 基于SV 40的附加型表达系统 将采用组织特异性和诱导性 启动子限制突变T抗原的表达,因此载体 扩增,到结肠肿瘤细胞。 具体目标2是确定 基于SV 40的附加型载体系统编码疱疹病毒的有效性 单纯病毒胸苷激酶体外杀伤肿瘤细胞。 暴露后 与GCV相比,将评估肿瘤细胞杀伤的特异性和效率。 在具体目标3中,将采用临床前结肠癌模型来 评价基于SV 40的附加体根除已建立肿瘤的能力 使用脂质体介导的基因转移在裸鼠中进行异种移植。 小鼠将被 随访肿瘤消退和存活率。 总之,本申请 支持关键的初始“原理验证”实验, 用于基因治疗的“肿瘤特异性”附加型载体和基因转移系统 结肠癌
英文摘要
DESCRIPTION: (Applicant's Abstract) The applicant's laboratory has recently developed a novel SV40-based episomal expression vector for human gene therapy applications that is predicted to be safe while permitting high copy replication in human cells. This episomal plasmid utilizes a specifically designed SV40 large T antigen mutant to drive extrachromosomal replication in human cells while eliminating the undesired ability of large T antigen to bind and inactivate host p53 and RB tumor suppressor gene proteins. Because this vector replicates to thousands of copies by 2-3 days after gene transfer, the expression system is predicted to safely express target genes at higher levels per cell than any currently published gene therapy vector. To further modify this vector to include appropriate safety and replication-control elements, the applicant proposes to develop a novel "colon cancer-specific" expression system which will amplify extrachromosomally and express target genes only in tumor cells. Specific Aim 1 is to develop a noninfectious, safety-modified SV40 based episomal expression system to permit external control of tumor-specific vector amplification and gene expression. An SV40-based episomal expression system will be constructed which employs both tissue-specific and inducible promoters to limit expression of mutant T antigen, and hence vector amplification, to colon tumor cells. Specific Aim 2 is to determine the effectiveness of the SV40-based episomal vector system encoding herpes simplex virus thymidine kinase to kill tumor cells in vitro. After exposure to GCV, the specificity and efficiency of tumor cell kill will be evaluated. In Specific Aim 3 a preclinical colon cancer model will be employed to evaluate the ability of SV40-based episomes to eradicate established tumor xenografts in nude mice using liposome-mediated gene transfer. Mice will be followed for tumor regression and survival. In summary, this application supports key, initial "proof-of-principle" experiments to evaluate "tumor-specific" episomal vectors and gene transfer systems for gene therapy of colon cancer.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Intrapulmonary Gene Transfer Using Compacted DNA
  • 批准号:
    6401494
  • 项目类别:
  • 资助金额:
    $10.0万
  • 财政年份:
    2001
  • 负责人:
    MARK J COOPER
  • 依托单位:
VACCINATION BY TOPICAL APPLICATION OF CONDENSED DNA
  • 批准号:
    6211596
  • 项目类别:
  • 资助金额:
    $10.0万
  • 财政年份:
    2000
  • 负责人:
    MARK J COOPER
  • 依托单位:
EPISOMAL VECTORS FOR BREAST CANCER GENE THERAPY
  • 批准号:
    6210668
  • 项目类别:
  • 资助金额:
    $9.95万
  • 财政年份:
    2000
  • 负责人:
    MARK J COOPER
  • 依托单位:
EPISOMAL VECTORS FOR COLON CANCER GENE THERAPY
  • 批准号:
    2633947
  • 项目类别:
  • 资助金额:
    $4.9万
  • 财政年份:
    1997
  • 负责人:
    MARK J COOPER
  • 依托单位:
海外基金