Development of cationic histone deacetylase inhibitors as enhancer of gene transfection and expression

脂质体转染是目前最常用的基因转染方法，具有安全、简便等优点。然而，用这种方法转染的基因的表达效率远低于用病毒载体。因此，我们试图开发高效的脂质转染增强剂。根据这一目标，我们完成了脂质转染增强剂的开发，其使基因的表达比对照增强高达23倍。增强子的结构基于组蛋白去乙酰化酶（HDAC）抑制剂，其增加细胞核中组蛋白的乙酰化水平，从而导致转录效率的增强。HDAC抑制剂还抑制HDAC_s的胞质同工酶HDAC 6，以促进转染基因向细胞核的转运。这也可能有助于增强转染基因的表达。

Lipofection is the most versatile transfection methods to transfect genes into mammalian cells, because of its safety and its handiness. However, the expression efficiency of the transfected genes with this method is much lower than that with viral vector. We therefore attempted to develop highly efficient enhancer for lipofection. According to this objective, we accomplished the development of lipofection enhancers which enhance the expression of genes up to 23 times more than that of control. Structure of the enhancer is based on histone deacetylase(HDAC) inhibitors, which increase acetylation level of histone in nucleus resulting in the enhancement of transcription efficiencies. HDAC inhibitors also inhibit a cytosolic isozyme of HDAC_s, HDAC6, to facilitate transportation of transfected genes to the nucleus. This may also contribute to the enhancement of the transfected gene expression.