TARGETED GENE THERAPIES FOR AIDS
艾滋病靶向基因治疗
基本信息
- 批准号:3144880
- 负责人:
- 金额:$ 17.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-08-01 至 1993-05-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS AIDS therapy Alphaherpesvirinae CD4 molecule acyclovir antiAIDS agent avidin biotin cytosine arabinoside dihydroxypropoxymethylguanine drug administration routes gene expression gene therapy genetic manipulation genetic markers genetic promoter element human immunodeficiency virus 1 immunoconjugates laboratory mouse liposomes lysine monoclonal antibody nonhuman therapy evaluation nucleic acid repetitive sequence protein kinase thymidine tissue /cell culture transfection vascular endothelium
项目摘要
We propose to deliver DNA to normal cells for potential treatment and
prevention of AIDS. ph-sensitive liposomes and poly-L-lysine linked with
specific ligands such as antibody will be used as target-specific delivery
vehicles for the exogenous DNA. Two approaches will be taken. In the first,
soluble CD4 gene will be delivered to the vascular endothelial cells.
Production and secretion of soluble CD4 by the endothelial cells is
expected to block the infectious activity of HIV. We will take advantage of
a monoclonal antibody specific for the pulmonary endothelial cells to
deliver the soluble CD4 gene in a mouse model. The soluble CD4 gene will be
placed under the control of a regulatable promoter such that the production
of the soluble CD4 could be controlled by the administration of a simple
drug. In the second approach we will deliver the thymidine kinase (TK) gene
of the Herpes Simplex Virus (HSV) to CD4+ normal cells. The TK gene will be
placed under the control of LTR of HIV-1 such that the gene will be
expressed at a significant level only when the cell is infected with HIV.
Production of large amounts of HSVTK in the infected cells would then make
the cells sensitive to drugs which are specific substrates for HSVTK, such
as DHPG and acyclovir. The cellular and viral DNA syntheses of the infected
cells would be inhibited by these drugs. This approach is potentially a
preventative as well as a therapeutic treatment for AIDS. The virtue of the
approach lies in three levels of safety guard of the treatment due to: (a)
the specificity of the delivery vehicles, (b) the activation of gene
expression by HIV infection, and (c) the opportunity to fine-tune the
therapeutic efficacy vs. toxicity by manipulating the drug dose and
administration regimen. Thus, the project addresses one of the most crucial
aspects of genetic therapy, i.e. safety of the treatment.
我们建议将DNA输送到正常细胞中进行潜在的治疗
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cationic liposomes enhance targeted delivery and expression of exogenous DNA mediated by N-terminal modified poly(L-lysine)-antibody conjugate in mouse lung endothelial cells.
阳离子脂质体增强由 N 端修饰的聚(L-赖氨酸)-抗体缀合物介导的外源 DNA 在小鼠肺内皮细胞中的靶向递送和表达。
- DOI:10.1016/0167-4781(92)90030-4
- 发表时间:1992
- 期刊:
- 影响因子:0
- 作者:Trubetskoy,VS;Torchilin,VP;Kennel,S;Huang,L
- 通讯作者:Huang,L
Characterization and kinetics of MHC class I-restricted presentation of a soluble antigen delivered by liposomes.
- DOI:10.1016/s0171-2985(11)80282-2
- 发表时间:1994-02
- 期刊:
- 影响因子:2.8
- 作者:F. Zhou;Simon C Watkins;L. Huang
- 通讯作者:F. Zhou;Simon C Watkins;L. Huang
Delivery of protein antigen to the major histocompatibility complex class I-restricted antigen presentation pathway.
- DOI:10.3109/10611869509059210
- 发表时间:1995
- 期刊:
- 影响因子:4.5
- 作者:F. Zhou;L. Huang
- 通讯作者:F. Zhou;L. Huang
Monophosphoryl lipid A enhances specific CTL induction by a soluble protein antigen entrapped in liposomes.
单磷酰脂质 A 通过包裹在脂质体中的可溶性蛋白抗原增强特异性 CTL 诱导。
- DOI:10.1016/0264-410x(93)90076-a
- 发表时间:1993
- 期刊:
- 影响因子:5.5
- 作者:Zhou,F;Huang,L
- 通讯作者:Huang,L
Immunotargeting of liposomes containing lipophilic antitumor prodrugs.
含有亲脂性抗肿瘤前药的脂质体的免疫靶向。
- DOI:10.1023/a:1018933632318
- 发表时间:1993
- 期刊:
- 影响因子:3.7
- 作者:Mori,A;Kennel,SJ;Huang,L
- 通讯作者:Huang,L
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{{ truncateString('Leaf Huang', 18)}}的其他基金
Nano Approaches to Modulate Host Cell Response for Cancer Therapy
调节宿主细胞反应以进行癌症治疗的纳米方法
- 批准号:
8960618 - 财政年份:2015
- 资助金额:
$ 17.7万 - 项目类别:
Project 1: Nanotherapies for Vemurafenib Resistant Melanoma
项目 1:维莫非尼耐药黑色素瘤的纳米疗法
- 批准号:
8960620 - 财政年份:2015
- 资助金额:
$ 17.7万 - 项目类别:
Therapeutic Targeting of the Ras Pathway By Nanoparticle Delivery of siRNA
通过 siRNA 纳米颗粒递送来治疗 Ras 通路
- 批准号:
8540374 - 财政年份:2013
- 资助金额:
$ 17.7万 - 项目类别:
Nanocrystals for the Treatment of Multidrug Resistance in Cancer
用于治疗癌症多药耐药性的纳米晶体
- 批准号:
8680176 - 财政年份:2011
- 资助金额:
$ 17.7万 - 项目类别:
Therapeutic Targeting of the Ras Pathway By Nanoparticle Delivery of siRNA
通过 siRNA 纳米颗粒递送来治疗 Ras 通路
- 批准号:
7982953 - 财政年份:2010
- 资助金额:
$ 17.7万 - 项目类别:
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