CAREER: Engineering Recombinant Lentiviruses for Cystic Fibrosis Gene Therapy

这项研究的目的是进一步了解慢病毒与细胞的相互作用，长期目标是开发可用于囊性纤维化基因治疗的改良慢病毒。 具体来说，本研究的目标是开发一种靶向慢病毒载体，并检查导致最大转染的细胞内途径。 本研究的具体任务包括：（1）验证通过将护送蛋白掺入病毒的脂质双层中可以改善慢病毒基因转移的假设，（2）定量分析护送蛋白对感染的影响，以及（3）将慢病毒工程化为极化上皮细胞顶端表面上的靶向受体。 从这项研究中获得的知识可以帮助设计下一代慢病毒载体，这将有助于人类基因治疗方案。

0134409Le DouxThe objective of the proposed research is to develop greater understanding of lentivirus-cell interactions, with the long-range goal of developing improved lentivirues that will be useful for cystic fibrosis gene therapy. Specifically, the goal of this research is to develop a targeted lentiviral vector and to examine the intracellular pathway that leads to maximal transfection. The specific tasks of this research include: (1) the test of the hypothesis that lentivirus gene transfer can be improved by incorporating escort proteins into the lipid bilayer of the viruses, (2) the quantitative analysis of the effect of the escort proteins on infection, and (3) the engineering of lentiviruses to target receptors on the apical surfaces of polarized epithelial cells. The knowledge gained from this research could help the design of the next generation of lentivirus vectors that would be useful for human gene therapy protocols.