Salivary Gland-Based Gene Therapy for Lysosomal Storage Diseases

基于唾液腺的溶酶体贮积病基因治疗

基本信息

批准号：
7814758
负责人：
Michael J. Passineau
金额：
$ 43.4万
依托单位：
ALLEGHENY-SINGER RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-23 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7814758
关键词：
Adenovirus Vector Animal Model Animals Biodistribution Biomedical Engineering Blood Blood Circulation Budgets Cells Characteristics Climate Clinical Trials Collaborations DNA Data Dependovirus Disadvantaged Dose Enzymes Evaluation Fabry Disease Frequencies Galactosidase Gases Gene Delivery Gene Expression Gene Transfer Genes Grant Hand Human Humoral Immunities Immune response Inflammation Institution Intervention Laboratories Link Lysosomal Storage Diseases Mainstreaming Mammals Mechanics Methods Microbubbles Microbubbles Ultrasound Contrast Medium Molecular Analysis Mouth Diseases Mus Non-Viral Vector Oral Organ Parents Performance Pharmaceutical Preparations Phase Physiological Plasma Plasmids Relative (related person)Research Research Personnel Running Safety Saliva Salivary Glands Sampling Schools System Systemic disease Technology Testing Therapeutic Time Tissues Titrations Transgenes Translations Treatment Protocols Ultrasonic Therapy Ultrasonography Universities Viral Viral Genes Viral Vector Visit Work Xerostomia adenoviral-mediated analytical method base experience gene therapy graduate student indexing non-viral gene delivery parent project plasmid DNA pre-clinical sonoporation uptake vector viral gene delivery

Adenovirus Vector Animal Model Animals Biodistribution Biomedical Engineering Blood Blood Circulation Budgets Cells Characteristics Climate Clinical Trials Collaborations DNA Data Dependovirus Disadvantaged Dose Enzymes Evaluation Fabry Disease Frequencies Galactosidase Gases Gene Delivery Gene Expression Gene Transfer Genes Grant Hand Human Humoral Immunities Immune response Inflammation Institution Intervention Laboratories Link Lysosomal Storage Diseases Mainstreaming Mammals Mechanics Methods Microbubbles Microbubbles Ultrasound Contrast Medium Molecular Analysis Mouth Diseases Mus Non-Viral Vector Oral Organ Parents Performance Pharmaceutical Preparations Phase Physiological Plasma Plasmids Relative (related person)Research Research Personnel Running Safety Saliva Salivary Glands Sampling Schools System Systemic disease Technology Testing Therapeutic Time Tissues Titrations Transgenes Translations Treatment Protocols Ultrasonic Therapy Ultrasonography Universities Viral Viral Genes Viral Vector Visit Work Xerostomia adenoviral-mediated analytical method base experience gene therapy graduate student indexing non-viral gene delivery parent project plasmid DNA pre-clinical sonoporation uptake vector viral gene delivery

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项目摘要

DESCRIPTION (provided by applicant): This Competitive Revision Application for 4R00DE018188-02 proposes to expand the parent project to include a non-viral method of gene delivery based upon ultrasound destruction of DNA-associated microbubbles. This ultrasound-assisted gene transfer (UAGT) works differently from the viral-based methods of the parent project, but the end result, gene transfer to the salivary gland is the same. Therefore, this supplement is proposed as a parallel but equivalent track, bringing in a co-investigator from within the Pi's affiliated institution who has almost twenty years of experience with ultrasoundmicrobubble technology. Figure 1 illustrates the relationship of the parent project and proposed supplement. By executing the parent project and the proposed supplemental research plan in concert, we will be able to leverage the existing expertise acquired in the physiological and molecular analysis of salivary gland-based gene therapy for Fabry disease. This will create a climate where the translational potential of both viral and non-viral gene transfer methods can be objectively compared under tightly controlled conditions. With salivary gland-based gene therapy now in a Phase 1 human clinical trial, such comparisons are imperative if long-term gene expression in the salivary gland of humans is to be achieved. The major mechanism for cementing collaboration between the Pl and the Co-l is the support of a floating graduate student who will participate in every step of the proposed supplemental project. This mechanism will link Dr. Wheatley's expertise in the construction and destruction of ultrasound microbubble contrast agents with Dr. Passineau's gene therapy laboratory. The proposed budget includes allocation for this graduate student, based in the Drexel University School of Biomedical Engineering, to make frequent extended visits to Pittsburgh for animal work and sample analysis.

描述（由申请人提供）：4R00DE018188-02的此竞争性修订申请提议将父项目扩展，以包括基于DNA相关微泡的超声破坏的非病毒基因递送方法。这种超声辅助基因转移（UAGT）的作用与基于母体项目的基于病毒的方法不同，但是最终结果，基因转移到唾液腺相同。因此，该补充剂被认为是一条平行但同等的轨道，从PI附属机构内部引入了一个共同研究员，该机构在超声波泡技术方面拥有将近二十年的经验。图1说明了父项目和拟议补充的关系。通过执行父项目和拟议的补充研究计划，我们将能够利用基于唾液腺的基因疗法用于Fabry Disease的生理和分子分析中获得的现有专业知识。这将创造一个气候，在这种气候下，在严格控制的条件下，可以客观地比较病毒和非病毒基因转移方法的翻译潜力。现在，在一项1期人类临床试验中，基于唾液腺基因疗法，如果要实现长期基因表达，则必须进行这种比较。巩固PL与Co-L之间合作的主要机制是浮动研究生的支持，该研究生将参加拟议的补充项目的每一步。这种机制将链接惠特利博士在建设和破坏超声波方面的专业知识微泡与Passineau博士的基因治疗实验室的对比剂。拟议的预算包括基于德雷克塞尔大学生物医学工程学院的这位研究生的分配，以便频繁地延长访问匹兹堡进行动物工作和样本分析。