KIDNEY SPECIFIC, LIPOSOME/POLYCATION MEDIATED THERAPY

肾脏特异性脂质体/聚阳离子介导治疗

• 批准号: 2905974
• 负责人: YEONG-HAU H. LIEN
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905974
• 关键词: carbonate dehydratase; cations; congenital kidney disorder; disease /disorder model; enzyme deficiency; gene expression; gene therapy; genetic promoter element; immunocytochemistry; laboratory mouse; liposomes; nonhuman therapy evaluation; polyion; polymerase chain reaction; renal tubule acidosis; tissue /cell culture; transfection

DESCRIPTION (Adapted from the Applicant's Abstract): The ultimate goal of this proposal is to develop gene therapy for the treatment of hereditary kidney diseases. The carbonic anhydrase (CA) II deficient mouse is an ideal model for kidney-specific gene therapy since it manifests renal tubular acidosis and effects of gene therapy can be easily monitored. CA II is an enzyme present in cells of the kidney and other organs such as the brain and bones, and is important for acid-base homeostasis at both cellular and whole body levels. The investigators have developed a novel approach by infusing the CA II gene, driven by a viral promoter, into the urinary space of the kidney of the CA II deficient mice using liposomes as carriers, and shown a transient (3 week) correction of renal tubular acidosis. During this grant period, new strategies will be tested to improve the efficacy and duration of gene expression using this gene therapy model. Specifically, the goals will be: 1) to add polycations, polymers of positive-charged organic compounds such as basic amino acids, to the liposome delivery system in order to enhance the transfection efficiency in vivo. These polycations may serve as signals for the therapeutic gene to be delivered to the nucleus; 2) to replace the viral promoter of the therapeutic gene with the CA II promoter in order to produce a cell-specific, regulatable, and long-term gene expression in mice; 3) to evaluate the safety of the liposome/polycation-mediated gene therapy in mice; and 4) to determine whether gene therapy in CA II deficient mice will convert the phenotypical changes associated with CA II deficiency, i.e., up-regulation of CA IV, and depletion of intercalated cells, which are responsible for acid secretion in the kidney. It is hoped that results obtained from the proposed study will lead to an optimum gene therapy suitable for future clinical trials on a broad range of renal diseases in humans.

描述（改编自申请人摘要）：的最终目标

项目成果

Bilateral symmetry of biomechanical properties in mouse femora.

小鼠股骨生物力学特性的双侧对称性。

• DOI: 10.1016/j.medengphy.2003.11.002
• 发表时间: 2004
• 期刊: Medical engineering & physics.
• 作者: Margolis,DavidS;Lien,Yeong-HauH;Lai,Li-Wen;Szivek,JohnA
• 通讯作者: Szivek,JohnA

Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy.

通过基因治疗纠正碳酸酐酶 II 缺陷小鼠的肾小管酸中毒。

• DOI: 10.1172/jci1694
• 发表时间: 1998
• 期刊: The Journal of clinical investigation
• 作者: Lai,LW;Chan,DM;Erickson,RP;Hsu,SJ;Lien,YH
• 通讯作者: Lien,YH

Cytoprotective effects of calbindin-D(28k) against antimycin-A induced hypoxic injury in proximal tubular cells.

• DOI: 10.1016/s0024-3205(02)01710-1
• 发表时间: 2002-06
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Ming-Ju Wu;L. Lai;Y. Lien

Gene therapy for renal diseases.

肾脏疾病的基因治疗。

• 发表时间: 1997
• 期刊: Kidney international. Supplement.
• 作者: Lien,YH;Lai,LW
• 通讯作者: Lai,LW

Entering the gene therapy era.

进入基因治疗时代。

• 发表时间: 1999
• 期刊: Journal of the Formosan Medical Association = Taiwan yi zhi
• 作者: Lien,YH;Lai,LW
• 通讯作者: Lai,LW