STERIC-STABILIZED LIPOSOMES FOR SYSTEMIC GENE DELIVERY

用于全身基因递送的空间稳定脂质体

• 批准号: 6232451
• 负责人: KENNETH J LONGMUIR
• 金额: $ 14.56万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-15 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6232451
• 关键词: biotechnology; gene delivery system; gene expression; histology; laboratory mouse; liposomes; nonhuman therapy evaluation; pharmacokinetics; technology /technique development

DESCRIPTION: (modified from applicant's abstract) The long-term objective is to develop a non-viral, liposomal gene delivery system appropriate for systemic delivery in vivo. This proposed delivery system does not use cationic lipids (the most common class of liposome formulations for gene delivery in use today) but instead uses a formulation strategy similar to long-circulating, sterically-stabilized liposomes currently in use for intravenous drug delivery. The principal hypothesis is that a sterically-stabilized gene delivery system will exhibit one or more of the following advantages over current gene delivery formulations: 1) Prolonged circulation times, leading to a more uniform organ and tissue distribution of gene expression, 2) increased ability to extravasate from vascular beds, leading to enhanced gene expression in cell types other than endothelium, monocytes, and macrophages, 3) preferential accumulation at sites of tumors within organs and tissues, 4) a reduction of inflammatory and other cytotoxic effects currently observed with cationic lipid formulations, and most importantly, 5) gene expression without the necessity for cell division. The proposal has three specific aims to be achieved during the two-year "Pilot and Feasibility Study": 1) A sterically-stabilized liposome formulation will be modified and tested for effective in vivo delivery using and adult mouse model. 2) Gene expression, pharmokinetics, and biodistribution will be assessed for prolonged circulation times. 3) Organ tissues will be examined histologically to assess gene expression in cell types outside the vasculature.

描述：（根据申请人摘要进行修改）长期目标是 开发适合全身性的非病毒，脂质体基因输送系统 在体内交付。该建议的输送系统不使用阳离子脂质 （当今使用的基因输送的最常见类型的脂质体配方） 而是使用类似于长期循环的公式策略， 目前正在使用静脉注射药物的脂质体。 主要假设是一个稳定的基因递送系统 将在当前基因递送中表现出以下优势的一个或多个优势 配方：1）长时间的循环时间，导致器官更均匀 和基因表达的组织分布，2）增加外观的能力 从血管床，导致细胞类型中的基因表达增强 比内皮，单核细胞和巨噬细胞，3）在 器官和组织内的肿瘤部位，4）炎症和 目前使用阳离子脂质制剂观察到的其他细胞毒性作用， 最重要的是，5）基因表达无需细胞 分配。 该提案在为期两年的“飞行员”中实现了三个具体目标 和可行性研究”： 1）将修改并测试一个稳定的脂质体配方 有效使用和成人小鼠模型在体内递送。 2）将评估基因表达，药理和生物分布 长时间的循环时间。 3）将在组织学上检查器官组织以评估基因表达 脉管系统外的细胞类型。