Development of topical gene delivery system for clinical application
临床应用局部基因递送系统的开发
基本信息
- 批准号:15590133
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Gene therapy is a useful treatment for curing inborn and acquired diseases. The eye has a number of advantages as a target organ for gene delivery. The use of non-viral vectors attracts great interests for in vivo gene delivery because they lack some of the risks inherent in viral vector systemsWe have investigated the transfection activity of plasmid DNA (pDNA)/cationic liposome complexes to the eye in rabbits. Among the transfection experiments with various lipids, pDNA complexed with DOTMA/Chol liposomes showed the highest transfection activity after intravitreal injection. The complexes at a charge raio of +2.0 produced maximal gene expression in the eye. In conlusion, optimizing the lipid composition of cationic liposomes and the charge ratio of pDNA/cationic liposome complexes should enhance the transfection efficiency to the eye.We have examined the effect of blood components on gene delivery with polyethyleneimine (PEI) in a human endothelial cell line. The transfection activity with pDNA/PEI complex was markedly decreased in the presence of fetal bovine serum, bovine serum albumin, human blood, human plasma, cholesterol and fatty acids, although it was not affected by lecithin and bile salts. Ternary complexes using polyanion could decrease the influence of blood components on gene expression. On the other hand, the transfection activity with pDNA/PEI complex was increased 2-3 times by the presence of glucose. We also found that the gene expression of pDNA/PEI complex and pDNA/liposomes complex was influenced by the disease such as hepatitis.We have developed the ocular pharmacokinetic/pharmacodynamic (PK/PD) model of model drug, bunazosin, on the basis of the concentration-time profiles and hypotensive profiles of bunazosin. The PK/PD models can predict the concentrations of bunazosin in the ocular tissues and its hypotensive effect after instillation and ocular injection. This PK/PD model must be useful for designing the gene delivery system.
基因治疗是治疗先天性和后天性疾病的有效手段。眼睛作为基因递送的靶器官具有许多优点。11非病毒载体的使用由于其不存在病毒载体系统固有的一些风险而引起了人们对体内基因传递的极大兴趣。在各种脂质体的转染实验中,与DOTMA/Chol脂质体复合的pDNA在玻璃体内注射后显示出最高的转染活性。电荷比为+2.0的复合物在眼睛中产生最大的基因表达。因此,优化阳离子脂质体的脂质组成和pDNA/阳离子脂质体复合物的电荷比可以提高基因转染效率。我们研究了血液成分对聚乙烯亚胺(PEI)基因转染人内皮细胞系的影响。当存在胎牛血清、牛血清白蛋白、人血、人血浆、胆固醇和脂肪酸时,pDNA/PEI复合物的转染活性显著降低,但卵磷脂和胆汁盐对pDNA/PEI复合物的转染活性无影响。聚阴离子三元配合物可降低血液成分对基因表达的影响。另一方面,葡萄糖的存在使pDNA/PEI复合物的转染活性增加2-3倍。我们还发现pDNA/PEI复合物和pDNA/脂质体复合物的基因表达受肝炎等疾病的影响,在此基础上建立了模型药物布那唑嗪的眼药动学/药效学(PK/PD)模型。PK/PD模型可预测布那唑嗪滴眼和眼内注射后眼组织中的药物浓度及其消肿作用。这一PK/PD模型对基因传递系统的设计具有一定的指导意义。
项目成果
期刊论文数量(40)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Unilateral kidney-selective gene transfer following the administration of naked plasmid DNA to the kidney surface in mice
将裸质粒 DNA 施用于小鼠肾脏表面后的单侧肾脏选择性基因转移
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Ryu Hirayama;Hitoshi Sasaki;Junzo Nakamura et al.
- 通讯作者:Junzo Nakamura et al.
Mugen Teshima, Mikiro Nakashima, Hitoshi Sasaki et al.: "Prednisolone retention in integrated liposomes by chemical approach and pharmaceutical approach"Journal of Controlled Release. 発表予定. (2004)
Mugen Teshima、Mikiro Nakashima、Hitoshi Sasaki 等人:“通过化学方法和药物方法保留泼尼松龙”《控释杂志》(2004 年)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Effect of solution composition of plasmid DNA on gene transfection following liver surface administration in mice.
质粒 DNA 溶液组成对小鼠肝表面给药后基因转染的影响。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:R.Hirayama;S.Fumoto;K.Nishida;M.Nakashima;H.Sasaki;J.Nakamura
- 通讯作者:J.Nakamura
Mechanism of permeability-enhancing effect of EDTA and bolic acid on the corneal penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5-carboxylic acid monohydrate (CS-088).
EDTA和酚酸对4-[1-羟基-1-甲基乙基]-2-丙基-1-[4-[2-[四唑-5-基]苯基]苯基角膜渗透的增透作用机制
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:T.Kikuchi;M.Suzuki;A.Kusai;K.Iseki;H.Sasaki;K.Nakashima
- 通讯作者:K.Nakashima
Ocular pharmacokinetic/pharmacodynamic modeling for bunazosin after instillation into rabbits
布那佐辛滴入家兔后眼部药代动力学/药效学模型
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Koji Sakanaka;Junzo Nakamura;Hitoshi Sasaki et al.
- 通讯作者:Hitoshi Sasaki et al.
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SASAKI Hitoshi其他文献
SASAKI Hitoshi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SASAKI Hitoshi', 18)}}的其他基金
Development of new nucleic acid medicines for intractable respiratory diseases
呼吸道难治性疾病核酸新药开发
- 批准号:
18H02589 - 财政年份:2018
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
A study on learning support system to maintain and improve the motivation by realizing the Learner's growth
通过实现学习者成长来维持和提高学习动机的学习支持系统研究
- 批准号:
26350286 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the novel technique intended to the prophylaxis and treatment of neglected tropical diseases
开发旨在预防和治疗被忽视的热带病的新技术
- 批准号:
26293034 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel gene therapy targeting age-related macular degeneration
针对年龄相关性黄斑变性的新型基因疗法的开发
- 批准号:
23659813 - 财政年份:2011
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
The development of self-assembly nano-devices based on electrostatic interaction and the application to selective drug delivery
基于静电相互作用的自组装纳米器件的开发及其在选择性药物输送中的应用
- 批准号:
21390010 - 财政年份:2009
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Research on a infrastructure for the development of the OSS technical education and learning support systems
OSS技术教育和学习支持系统开发基础设施研究
- 批准号:
20500845 - 财政年份:2008
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Influence of disease stage and pharmacotherapy on gene delivery
疾病阶段和药物治疗对基因递送的影响
- 批准号:
18590143 - 财政年份:2006
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Is a color processed with a right hemispheric dominance?
颜色是由右半球优势处理的吗?
- 批准号:
15500136 - 财政年份:2003
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional recovery after nerve transplantation to optic nerve
视神经神经移植术后功能恢复
- 批准号:
13671837 - 财政年份:2001
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Effects of color vision on emotion.
色觉对情绪的影响。
- 批准号:
10835010 - 财政年份:1998
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
相似海外基金
I-Corps: Translation Potential of Rapid In-situ Forming Gel for Local Gene Delivery
I-Corps:快速原位形成凝胶用于局部基因传递的转化潜力
- 批准号:
2410778 - 财政年份:2024
- 资助金额:
$ 2.24万 - 项目类别:
Standard Grant
CAREER: Developing Ultrasound-Programmable 3D-Printed Biomaterials for Spatiotemporal Control of Gene Delivery
职业:开发用于基因传递时空控制的超声波可编程 3D 打印生物材料
- 批准号:
2339254 - 财政年份:2024
- 资助金额:
$ 2.24万 - 项目类别:
Continuing Grant
Creating an optimized and scalable production platform in suspension adapted serum-free HEK293 cells for rAAV gene delivery using a Design-of-Experime
使用实验设计在悬浮适应的无血清 HEK293 细胞中创建优化且可扩展的生产平台,用于 rAAV 基因递送
- 批准号:
2776049 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Studentship
Oncolytic virus bispecific gene delivery for high grade gliomas
用于高级别神经胶质瘤的溶瘤病毒双特异性基因递送
- 批准号:
10832350 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Mitigating the Immunogenicity of Engineered Aav Gene Delivery Vectors by Biomaterial-Driven Immunosuppression
通过生物材料驱动的免疫抑制减轻工程化 Aav 基因递送载体的免疫原性
- 批准号:
10741139 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Computationally-Inspired Design of Non-Viral Gene Delivery Vehicles for mRNA-Based Cystic Fibrosis Therapies
用于基于 mRNA 的囊性纤维化治疗的非病毒基因传递载体的计算启发设计
- 批准号:
10760605 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Non-viral gene delivery platforms for the treatment of Usher Syndrome Type 2A.
用于治疗 2A 型亚瑟综合症的非病毒基因递送平台。
- 批准号:
10578428 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Targeted Gene Delivery and Human Dendritic Cell Maturation Through a Novel Hybrid Biological-Biomaterial Vector System
通过新型混合生物-生物材料载体系统进行靶向基因递送和人类树突状细胞成熟
- 批准号:
10586414 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Advanced development of composite gene delivery and CAR engineering systems
复合基因递送和CAR工程系统的先进开发
- 批准号:
10709085 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Investigation of the internal structure of lipid nanoparticles for gene delivery
用于基因传递的脂质纳米粒子的内部结构研究
- 批准号:
ST/Y000587/1 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Research Grant