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Pseudotyping of retroviral vectors, methods for their production and their use for targeted gene transfer and selection of high processing capacity

机译:逆转录病毒载体的假分型,其生产方法及其在靶向基因转移和高加工能力中的应用

摘要

The invention relates to the pseudotyping of retroviral vectors with heterologous envelope proteins derived from the Paramyxoviridae family, genus Morbillivirus, and various uses of the resulting vector particles. The present invention is based on the unexpected and surprising finding that the incorporation of morbillivirus F and H proteins having truncated cytoplasmic tails into lentiviral vector particles, and the complex interaction of these two proteins during cellular fusion, allows for a superior and more effective transduction of cells. Moreover, these pseudotyped vector particles allow the targeted gene transfer into a given cell type of interest by modifying a mutated and truncated H protein with a single-chain antibody or ligand directed against a cell surface marker of the target cell.
机译:本发明涉及用衍生自副粘病毒科,麻疹病毒属的异源包膜蛋白对逆转录病毒载体进行假型化,以及所得载体颗粒的各种用途。本发明基于出乎意料和令人惊讶的发现,即,将具有截短的细胞质尾巴的麻疹病毒F和H蛋白掺入慢病毒载体颗粒中,以及这两种蛋白在细胞融合过程中的复杂相互作用,使得能够更好地,更有效地转导大肠杆菌。细胞。而且,这些伪型载体颗粒通过用针对靶细胞的细胞表面标志物的单链抗体或配体修饰突变的和截短的H蛋白,使靶基因转移到感兴趣的给定细胞类型中。

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