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去唾液酸糖蛋白-聚赖氨酸偶联物靶向肝细胞的DNA命运

Fate of DNA targeted to hepatocytes by asialoglycoprotein polylysine conjugates.

作者信息

Wu G W, Chowdhury J R, Bommineni V R, Basu S K, Wu C H, Chowdhury N R

机构信息

Department of Medicine, University of Connecticut School of Medicine, Farmington 06030-1845, USA.

出版信息

Proc Assoc Am Physicians. 1995 Jul;107(2):211-7.

PMID:8624854
Abstract

The data indicate that partial hepatectomy results in a decrease in degradation of targeted DNA. This appears to be due to an inhibition of the endocytotic pathway shortly after hepatectomy and is associated with the accumulation of targeted DNA within a population of light endosomal vesicles. It is likely that these vesicles serve as a reservoir from which targeted DNA gradually escapes and can be found in the nucleus. The DNA targeted to liver is capable of expressing the marker gene, and the DNA in the vesicles is transfection competent, suggesting that a substantial portion is intact. Overall, the receptor-mediated delivery system is highly efficient in transporting foreign DNA to liver cells. Partial hepatectomy and the ensuing cellular events provide a means of inhibiting the degradative portion of the endocytotic pathway. Pharmacological agents that can mimic the cellular processes that occur after partial hepatectomy may be useful in increasing the duration of foreign gene expression without the trauma of surgery.

摘要

数据表明,部分肝切除会导致靶向DNA降解减少。这似乎是由于肝切除后不久内吞途径受到抑制,且与靶向DNA在一群轻型内体囊泡中的积累有关。这些囊泡可能充当了一个储存库,靶向DNA从其中逐渐逸出并可在细胞核中被发现。靶向肝脏的DNA能够表达标记基因,囊泡中的DNA具有转染能力,这表明大部分DNA是完整的。总体而言,受体介导的递送系统在将外源DNA转运到肝细胞方面效率很高。部分肝切除及随后的细胞事件提供了一种抑制内吞途径降解部分的方法。能够模拟部分肝切除后发生的细胞过程的药物制剂可能有助于延长外源基因表达的持续时间,而无需手术创伤。

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Proc Assoc Am Physicians. 1995 Jul;107(2):211-7.
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