CATIONIC LIPIDS FOR CFTR GENE THERAPY
用于 CFTR 基因治疗的阳离子脂质
基本信息
- 批准号:2518421
- 负责人:
- 金额:$ 17.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-09-30 至 2000-08-31
- 项目状态:已结题
- 来源:
- 关键词:aerosols chemical conjugate chloride channels clinical trials cystic fibrosis electrical potential gene expression gene therapy genotype human subject human therapy evaluation ion transport laboratory rabbit laboratory rat liposomes molecular polarity phosphatidylethanolamines plasmids polymerase chain reaction reporter genes respiratory epithelium tissue /cell culture transfection transfection /expression vector
项目摘要
Our laboratory has developed experience with cationic Liposome based gene
transfer. We have applied this methodology to CFTR delivery in preclinical
studies to human respiratory epithelial cells in vitro, as well as to
mammalian respiratory epithelium in vivo. In addition, preclinical studies
of gene transfer using cationic liposomes have rapidly led to development
of a human clinical trial of CFTR transfer using a DMRIE/DOPE vehicle.
These basic and preclinical developments have Created the need for a formal
means for initiating therapeutic, clinical trials involving CF patients.
This project intends to provide the resources necessary to develop and
complete a clinical trial of CFTR gene transfer to the nasal airway in 9 CF
patients using cationic Iiposomes. This study is the first step towards
future trials of liposome based CFTR therapy, including evaluation of
repeated nasal administration of CFTR, lower airway administration of
Iipid/DNA conjugates to CF patients, and studies of other cationic lipids
or lipid/DNA ratios during in vivo human gene administration. We will
perform clinical assays necessary to facilitate future human studies of CF
at the UAB center. These assays include 1) measurement of nasal potential
difference; 2) RT-PCR detection of normal CFTR mRNA following gene
transfer; 3) primary culture of airway epithelial cells following in vivo
gene transfer; and 4) CFTR mutation analysis. We will also examine the
mechanisms of gene delivery and expression underlying lipid based gene
transfer in vitro and in vivo. The principles and approaches developed
within this project will form a solid foundation for future studies of
liposomal CFTR gene therapy.
我们的实验室已经开发了基于阳离子脂质体的基因
转移我们已经将这种方法应用于临床前CFTR递送。
体外对人呼吸道上皮细胞的研究,以及
哺乳动物体内的呼吸上皮。此外,临床前研究
使用阳离子脂质体进行基因转移的研究迅速发展,
使用DMRIE/DOPE媒介物的CFTR转移的人类临床试验。
这些基础和临床前的发展创造了一个正式的需要,
启动涉及CF患者的治疗性临床试验的方法。
该项目旨在提供必要的资源,
在9例CF患者中完成了CFTR基因转移到鼻气道的临床试验
使用阳离子脂质体的患者。这项研究是迈向
基于脂质体的CFTR治疗的未来试验,包括评估
CFTR的重复鼻内给药,
CF患者的脂质/DNA缀合物,以及其他阳离子脂质的研究
或脂质/DNA比率。我们将
进行必要的临床试验,以促进未来的CF人体研究
在UAB中心。这些测定包括1)测量鼻电位
2)RT-PCR检测正常CFTR mRNA后基因
3)气道上皮细胞的原代培养,
基因转移;和4)CFTR突变分析。我们亦会研究
脂质基基因的基因传递和表达机制
体外和体内转移。制定的原则和办法
在这个项目中,将为未来的研究奠定坚实的基础,
脂质体CFTR基因治疗。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Components of human papillomavirus that activate transcription and support plasmid replication in human airway cells.
人乳头瘤病毒的成分,可在人呼吸道细胞中激活转录并支持质粒复制。
- DOI:10.1165/ajrcmb.20.5.3479
- 发表时间:1999
- 期刊:
- 影响因子:0
- 作者:Gadi,VK;Zou,N;Liu,JS;Cheng,S;Broker,TR;Sorscher,EJ;Chow,LT
- 通讯作者:Chow,LT
Relationship between airway ion transport and a mild pulmonary disease mutation in CFTR.
气道离子转运与 CFTR 中轻度肺部疾病突变的关系。
- DOI:10.1164/ajrccm.155.5.9154877
- 发表时间:1997
- 期刊:
- 影响因子:0
- 作者:Walker,LC;Venglarik,CJ;Aubin,G;Weatherly,MR;McCarty,NA;Lesnick,B;Ruiz,F;Clancy,JP;Sorscher,EJ
- 通讯作者:Sorscher,EJ
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Eric J SORSCHER其他文献
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{{ truncateString('Eric J SORSCHER', 18)}}的其他基金
Intratumoral generation of F-Ade to ablate low growth fraction HNSCC
瘤内生成 F-Ade 以消除低生长分数 HNSCC
- 批准号:
9311681 - 财政年份:2017
- 资助金额:
$ 17.87万 - 项目类别: