Leone P, Janson C G, McPhee S J, During M J
CNS Gene Therapy Center, Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Curr Opin Mol Ther. 1999 Aug;1(4):487-92.
The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant adeno-associated virus (AAV) vectors.
我们选择用来测试基因治疗策略的神经遗传原型疾病是卡纳万病（CD）。CD是一种常染色体隐性脑白质营养不良症，与大脑海绵状变性相关。目前，该病在受影响的先证者中无一例外都是致命的。CD的特征是天冬氨酸酰基转移酶（ASPA）基因突变，导致酶活性丧失。在这篇综述中，总结了关于CD病因和可能治疗方法的最新证据。特别是，我们讨论了代表病毒和脂质体技术最新进展的两种基因传递系统：一种新型阳离子脂质体-聚合物-DNA（LPD）复合物、DCChol/DOPE-鱼精蛋白，以及重组腺相关病毒（AAV）载体。
