CAREER: Real-Time Transport Phenomena of Non-Viral DNA Nanocarriers in Live Cells: A Research and Education Program

职业：活细胞中非病毒 DNA 纳米载体的实时传输现象：研究和教育项目

• 批准号: 0346716
• 负责人: Justin Hanes
• 金额: $ 40万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0346716&HistoricalAwards=false
• 关键词: CAREER; Real; Time; Transport; Phenomena

Justin S. HanesBES-0346716This proposed research seeks to quantify the rates and efficiencies of particle transport through potential intracellular rate-limiting barriers by using a imaging technique and particle tracking software. The specific aims are: (1) to investigate the effects of gene carrier physicochemical properties on the spatially- and temporally-dependent intracellular transport and accumulation of a variety of important non-viral gene carriers in human primary muscle and endothelial cells, (2) to determine the biological and/or biophysical mechanisms responsible for the intracellular gene carrier transport phenomena, and (3) to identify the effects of attaching combinations of important bioactive ligands to the gene carrier surface on the intracellular transport of the carriers, and correlate this with gene expression. The potential scientific insights to be gained from the proposed research may provide a rational basis for the improved design of new gene carriers capable of more efficient delivery to the cell nucleus. The ability to determine the transport behavior of a heterogeneous population of carriers on an individual carrier basis is critical since only a minute fraction of gene carriers applied to a cell ultimately reaches the nucleus. In addition, two innovative educational initiatives designed to recruit and retain young people, especially underprivileged and underrepresented students, into engineering careers are proposed. The first is a combined coursework and research program for undergraduates with an emphasis on technical communication skills and independent research. The second is a high school outreach research program targeted toward students that come from underprivileged families, or that are part of underrepresented groups in science and engineering.

贾斯汀·S HanesBES-0346716这项拟议的研究旨在通过使用成像技术和粒子跟踪软件来量化粒子通过潜在的细胞内限速屏障的转运速率和效率。具体目标是：（1）研究基因载体物理化学性质对多种重要的非病毒基因载体在人原代肌肉和内皮细胞中的空间和时间依赖性细胞内转运和积累的影响，（2）确定引起细胞内基因载体转运现象的生物学和/或生物物理学机制，和（3）鉴定将重要的生物活性配体的组合连接到基因载体表面对载体的细胞内转运的影响，并将其与基因表达相关联。从拟议的研究中获得的潜在科学见解可能为改进设计能够更有效地传递到细胞核的新基因载体提供合理的基础。在单个载体的基础上确定载体的异质群体的运输行为的能力是至关重要的，因为施加到细胞的基因载体中只有一小部分最终到达细胞核。此外，还提出了两项创新教育举措，旨在招募和留住年轻人，特别是弱势群体和代表性不足的学生，从事工程职业。第一个是为本科生提供的课程和研究计划，重点是技术沟通技能和独立研究。第二个是高中外展研究计划，针对来自贫困家庭的学生，或者是科学和工程领域代表性不足的群体。