期刊
BIOMATERIALS
卷 33, 期 5, 页码 1589-1595出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.10.082
关键词
Mitochondria; Mitochondrial drug delivery; Mitochondrial gene therapy; MITO-Porter; Membrane fusion; Mitochondrial DNA (mtDNA)
资金
- National Institute of Biomedical Innovation, Japan (NIBIO)
- Ministry of Education, Culture, Sports, Science and Technology of Japanese Government (MEXT)
- Grants-in-Aid for Scientific Research [22229001, 23680053] Funding Source: KAKEN
Mitochondrial dysfunction has been implicated in a variety of human diseases. It is now well accepted that mutations and defects in the mitochondrial genome form the basis of these diseases. Therefore, mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve such a strategy, it will be necessary to deliver therapeutic agents into mitochondria in living cells. We report here on an approach to accomplish this via the use of a Dual Function (DF)-MITO-Porter, aimed at the mitochondrial genome, so-called mitochondrial DNA (mtDNA). The DF-MITO-Porter, a nano carrier for mitochondrial delivery, has the ability to penetrate the endosomal and mitochondrial membranes via step-wise membrane fusion. We first constructed a DF-MITO-Porter encapsulating DNase 1 protein as a bioactive cargo. It was expected that mtDNA would be digested, when the DNase I was delivered to the mitochondria. We observed the intracellular trafficking of the carriers, and then measured mitochondrial activity and mtDNA-levels after the delivery of DNase I by the DF-MITO-Porter. The findings confirm that the DF-MITO-Porter effectively delivered the DNase 1 into the mitochondria, and provides a demonstration of its potential use in therapies that are selective for the mitochondrial genome. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据