A Novel Toolbox of Gene Expression Systems Applicable to Multimodality Molecular-Genetic Imaging

我的研究项目涉及一个名为分子遗传成像的新兴科学领域，该领域专注于开发基于DNA的分子，称为基因载体，以成像人体深处的细胞和分子。这些基因载体是在实验室中进行改造的，以制造被称为成像报告的分子，这些分子可以被各种成像扫描仪检测到，并有两个主要用途。首先，它们可以被设计成当它们被注射到体内时，它们允许人们看到特定细胞位于哪里，它们是如何行为的，以及它们的位置和数量是否会随着时间的推移而变化(S)。其次，人们可以使用这些载体来标记实验室中培养的细胞，这样当这些细胞被引入体内时，人们就可以进行成像，以跟踪它们在哪里结束以及它们如何与其他组织相互作用。推动这一领域向前发展的关键是基因载体的生产，这种载体可以使成像记者(S)处于尽可能高的水平，并且不会对正常细胞功能产生任何负面影响。通过这种方式，我们可以检测到尽可能少的细胞，而不会产生任何毒性影响。目前，我们还没有这种用于分子遗传成像应用的工具。考虑到这一根本限制，我的研究计划将开发一种新的工具箱，其中包括强大而无毒的基因载体，有助于克服这两个关键瓶颈。具体地说，我将开发和优化几个最先进的报告基因载体，称为微环(MC)、自我复制MC、整合酶缺陷慢病毒载体(IDLV)和自我复制IDLV；所有这些尖端载体在我的领域都没有被广泛探索。我还专注于开发表达多个记者的载体，这些载体可以用各种成像机检测到，因此它们将用于尽可能多的应用。我的长期目标是不断发展这些技术，并在动物模型中测试最优系统，这可能会对加拿大和世界各地的临床成像问题产生长期影响。总而言之，我的研究将解决与不同基因载体用于分子遗传成像的有效性和局限性有关的基本问题。考虑到学术界和工业界对分子遗传成像技术的新兴趣，我的项目处于有利地位，能够在重要试剂的创新中做出关键贡献。**

My research program deals with an emerging field of science called molecular-genetic imaging that focuses on the development of DNA-based molecules called gene vectors to image cells and molecules deep within the body. These gene vectors are engineered in the lab to make molecules called imaging reporters that are detectable with a variety of imaging scanners and have two main applications. First, they can be designed in a way that when they are injected into the body they permit one to see where specific cells are located, how they are behaving, and if their location(s) and numbers change over time. Secondly, one can use these vectors to tag cells grown in the lab so that when these cells are introduced into the body one can perform imaging to track where they end up and how they are interacting with other tissues. Critical to moving this field forward are the production of gene vectors that can make imaging reporter(s) at the highest possible levels and do not have any negative effects on normal cell function. This way we can detect the fewest number of cells possible without any toxic effects. Currently we do not have such tools for molecular-genetic imaging applications. With this fundamental limitation in mind, my research program will develop a new toolbox of powerful and non-toxic gene vectors that will help overcome these two critical bottlenecks. Specifically, I will develop and optimize several state-of-the-art reporter gene vectors called minicircles (MCs), self-replicating MCs, integrase-defective lentiviral vectors (IDLVs), and self-replicating IDLVs; all cutting-edge vectors that not been extensively explored in my field. I am also focused on developing vectors that express multiple reporters that are detectable with an assortment of imaging machines so they will be useful for as many applications as possible. My long-term goals are to continually evolve these technologies and test the optimal systems in animal models, with the potential for long-term impact in clinical imaging problems both in Canada and around the world. In summary, my research will address fundamental questions concerning the effectiveness and limitations of different gene vectors for molecular-genetic imaging. Considering the emerging interest in molecular-genetic imaging technologies in both academic and industrial settings, my program is well positioned to make critical contributions in the innovation of important reagents.**