Methamphetamine and HIV-1 Infection: Targeted Nanoparticles for Gene Silencing.

甲基苯丙胺和 HIV-1 感染：用于基因沉默的靶向纳米颗粒。

• 批准号: 7578893
• 负责人: JESSICA L REYNOLDS
• 金额: $ 15.4万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2013-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7578893
• 关键词: Abbreviations; Acquired Immunodeficiency Syndrome; Analysis of Variance; Antibodies; Arts; Basic Science; Binding; Bioinformatics; Biological Sciences; Biophotonics; Buffaloes; CD4 Positive T Lymphocytes; Cells; Chemicals; Chemistry; Clinical Medicine; Dendritic Cells; Development; Discipline; Drug abuse; Effectiveness; Environment; Fellowship; Funding; Galectin 1; Gene Proteins; Gene Silencing; General Hospitals; Genes; Goals; HIV-1; Highly Active Antiretroviral Therapy; Human; Image; Imaging Techniques; Immunologic Deficiency Syndromes; In Vitro; Infection; Institutes; Intervention; Kinetics; Knowledge; Laboratories; Laboratory Research; Lasers; Link; Magnetic Resonance; Medical; Medicine; Mentored Research Scientist Development Award; Methamphetamine; Methodology; Methods; Nanotechnology; National Research Service Awards; Pathogenesis; Peripheral Blood Mononuclear Cell; Polyethylene Glycols; Postdoctoral Fellow; Process; Protein Disulfide Isomerase; Public Health; Research; Research Personnel; Resolution; Retrovirology; Rhodamine; Rhodamines; Role; Roswell Park Cancer Institute; Scientist; Silicon Dioxide; Small Interfering RNA; Surface; System; T-Lymphocyte; Thioredoxin; Time; Toxic effect; Training; Transcript; Transfection; Universities; addiction; antibody conjugate; base; career; clinical application; drug of abuse; in vitro testing; indexing; innovation; insight; knock-down; macrophage; molecular imaging; monocyte; nanomaterials; nanoparticle; peroxiredoxin; photonics; protein expression; skills

DESCRIPTION (provided by applicant): Receipt of a K01 award will allow the applicant to successfully transition into an independent investigator by providing protected time for the acquistion of new knowledge and technical skills by undertaking further research in the rapidly advancing field of nanotechnology. The objective of this application is to bridge 2 scientific disciplines by integrating nanotechnology with research on the role of drug abuse in HIV-1 infections. The latter was the basis for the applicant's post-doctoral fellowship funded by a National Research Service Award. Additional training in nanotechnology will significantly assist the applicant to expand her research direction by applying this new expertise to the development of innovative methods to control HIV-1 infections associated with drug abuse. Under the sponsorship of Dr. Paras Prasad, an internationally known expert in nanomaterials, and with guidance from her co-sponsor Dr. Stanley Schwartz, known for his research in drugs of abuse and HIV-1 infections, the applicant will receive didactic and laboratory training in applying nanotechnology to biomedical applications. Bioconjugated nanoparticles have great potential for studying intracellular processes at the single-cell level using high-resolution imaging. This proposal will investigate the effectiveness of organically modified silica (ORMOSIL) nanoparticles as a platform to deliver small interfering (siRNA) targeted to specific genes (galectin-1, protein disulfide isomerase, thioredoxin and peroxiredoxin) relevant to HIV-1 infections whose expression has been shown by the applicant to be modulated by methamphetamine. The inertness and non-toxicity of ORMOSIL nanoparticles render them promising materials for biomedical and clinical applications. The interdisciplinary environment, involving both basic science (Chemistry) and clinical (Medicine) departments, supporting this project is unique with state of the art facilities. The research laboratories of the Department of Medicine in the Buffalo General Hospital are on the Buffalo-Niagara Medical Campus including the Center of Excellence in Bioinformatics and Life Sciences and the Roswell Park Cancer Institute. She also will utilize the facilities of the Institute for Lasers, Photonics and Biophotonics on the main campus of the University at Buffalo. The applicant's career goals are to become an independently funded, academic scientist, directing her own research laboratory. By bridging the fields of nanotechnology, addiction research, and retrovirology, these studies may yield an innovative and powerful, new methodology providing further insight into and new interventions for the serious public health issues of drug abuse and HIV-1 infections.

描述（由申请人提供）：获得K01奖励将使申请人通过在快速前进的纳米技术领域进行进一步研究，从而使申请人能够成功地过渡到独立研究者，从而获得新的知识和技术技能。该应用的目的是通过将纳米技术与药物滥用在HIV-1感染中的作用进行研究来桥接2个科学学科。后者是由国家研究服务奖资助的申请人博士后奖学金的基础。纳米技术的额外培训将通过将这种新专业知识应用于创新方法来控制与药物滥用相关的HIV-1感染来开发创新方法，从而大大帮助申请人扩大研究方向。在国际知名的纳米材料专家帕拉斯·普拉萨德（Paras Prasad）的赞助下，在她的共同发起人斯坦利·施瓦茨（Stanley Schwartz）博士的指导下，以其在滥用药物和HIV-1感染方面的研究而闻名，申请人将接受与生物典型应用的纳米技术有关的教学和实验室培训。生物偶联的纳米颗粒具有使用高分辨率成像在单细胞水平研究细胞内过程的巨大潜力。该提议将研究有机修饰的二氧化硅（Ormosil）纳米颗粒的有效性，作为提供针对特定基因（Galectin-1，蛋白质二硫化物异构酶，硫代蛋白蛋白质和过氧蛋白）的针对特定基因的小型干扰（siRNA）的平台，该平台与HIV-1相关的HIV-1感染与甲基甲基甲基化的表达相关。 Ormosil纳米颗粒的惰性和无毒性使它们成为生物医学和临床应用的有前途的材料。涉及基础科学（化学）和临床（医学）部门的跨学科环境，支持该项目在最先进的设施中是独一无二的。布法罗综合医院医学系的研究实验室位于布法罗 - 尼亚加拉医疗校园，包括生物信息学和生命科学卓越中心和罗斯威尔公园癌症研究所。她还将在布法罗大学主校园内利用激光，光子和生物光谱学研究所的设施。申请人的职业目标是成为一名独立资助的学术科学家，指导自己的研究实验室。通过弥合纳米技术，成瘾研究和逆转录病毒学领域，这些研究可能会产生一种创新且有力的新方法，从而为严重的药物滥用和HIV-1感染的严重公共卫生问题提供了进一步的了解和新干预措施。