公开(公告)号：US06436708B1

公开(公告)日：2002-08-20

申请号：US09202564

申请日：1999-02-08

申请人： Paola Leone ,  Matthew J. During ,  Frank L. Sorgi

发明人： Paola Leone ,  Matthew J. During ,  Frank L. Sorgi

IPC分类号： C12N1588

CPC分类号： C12N15/86 ,  A61K9/0085 ,  A61K9/1272 ,  A61K47/544 ,  A61K48/00 ,  A61K48/0041 ,  C12N9/88 ,  C12N15/87 ,  C12N15/88 ,  C12N2750/14143

摘要： A gene delivery system which. is both safe and results in long-term expression throughout the brain has been developed. A lipid-entrapped, polycation-condensed DNA (LPD) system has been developed for brain gene delivery, using an adeno-associated vial. (“AAV”) vector in which the transcription unit is flanked by the 145 bp inverted terminal repeats (ITR) of the adeno-associated virus. This AAV plasmid is more effective than a non-ITR containing plasmid in vivo. The results show that the LPD-AAV plasmid complexes efficiently transduce neurons and that gene expression can persist for over 10 months in the brain. Furthermore, the intraventricular delivery method with systemic hyperosmolality results in global gene delivery. The examples show that expression of the human aspartoacyclase (“ASPA”) gene in children with this metabolic disorder can be obtained over a period of many months to a year, with functional activity.

摘要翻译： 一种基因传递系统。 都是安全的，并导致长期表达，整个大脑已经开发出来。 已经开发了用于脑基因递送的脂质包埋的聚阳离子稠合DNA（LPD）系统，使用腺相关小瓶。 （“AAV”）载体，其中转录单位侧翼为腺相关病毒的145bp反向末端重复序列（ITR）。 该AAV质粒在体内比含有非ITR的质粒更有效。 结果表明，LPD-AAV质粒复合物有效转导神经元，并且基因表达可在脑中持续超过10个月。 此外，具有全身高渗性的心室内递送方法导致全球基因递送。 实施例表明，在具有这种代谢紊乱的儿童中，人类天冬酰胺酶（“ASPA”）基因的表达可以在多个月至一年的时间内获得，具有功能活性。