AN MRI CONTRAST AGENT THAT DETECTS GENE EXPRESSION

我们实验室开发了一种磁共振造影剂，它是一种体内基因表达指标。该试剂通过与常见的报告基因-半乳糖苷酶的酶切而激活。在体内观察到的基因表达模式可以为潜在的基因调控过程提供线索；这对于理解疾病的发病机制和治疗具有重要的影响。初步结果表明，该制剂在爪蟾胚胎系统中是非常有效的，其中该制剂通过显微注射引入。然而，在没有显微注射的情况下，细胞对药物的摄取或药物在组织中的分布情况知之甚少。为了进一步了解这种药物，我们建议研究其在细胞培养系统、小鼠肿瘤模型和转基因小鼠中的行为。我们将研究药物在这些系统中的运动和激活，研究脂质体递送系统的功效，并探讨药物的修饰如何影响其激活效率和运输特性。

Our laboratory has developed a magnetic resonance contrast agent that is an in vivo indicator for gene expression. This agent is activated by enzymatic cleavage with the common reporter gene, beta-galactosidase. The patterns of gene expression observed in vivo can yield clues to underlying gene regulation processes; this has important ramifications for understanding disease pathogenesis and therapy. Preliminary results show that the agent is very effective in a Xenopus embryo system, wherein the agent is introduced by microinjection. However, little is known about the uptake of the agent by cells, or the distribution of the agent in tissues in the absence of microinjection. In order to advance our understanding of this agent, we propose to study its behavior in cell culture systems, in a mouse tumor model, and in transgenic mice. We will examine the movement and activation of the agent in these systems, investigate the efficacy of liposomal delivery systems, and explore how modifications to the agent affect its activation efficiency and transport properties.