کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
592164 1453893 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of mitochondrial targeting plasmid DNA nanoparticles: Characterization and in vitro studies
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی شیمی کلوئیدی و سطحی
پیش نمایش صفحه اول مقاله
Development of mitochondrial targeting plasmid DNA nanoparticles: Characterization and in vitro studies
چکیده انگلیسی


• The development of gene therapy to treat mitochondrial DNA disorders is promising.
• We present rhodamine plasmid DNA nanoparticles with suitable size and morphology.
• Rhodamine fluorescence shows the internalization of nanoparticles into mitochondria.
• Mitochondrial targeted delivery was confirmed by fluorescence confocal microscopy.
• This work represents an important step in mitochondrial gene therapy.

Mutations in mitochondrial DNA are a frequent cause of metabolic and neuromuscular cytopathies and appear associated with Parkinson's and Alzheimer's diseases, diabetes, cancer and, with both premature aging and mortality worldwide. Although considered greater scourges of modern life, there is no clear consensus regarding an effective therapeutics. The development of gene therapy to treat mitochondrial DNA disorders offers a promising approach. Our group followed a co-precipitation method to formulate mitochondrial targeted rhodamine plasmid DNA based delivery systems, as a first step, for mitochondrial gene therapy implementation. To test the influence of plasmid size and composition on both the interaction with mitochondria and transfection efficiency, three different plasmids (pCAG-GFP, pcDNA3-myc-FLNa S2152A and pVAX1-LacZ) have been used. All systems are biocompatible and have suitable size and morphology for gene delivery purposes. Rhodamine associated fluorescence in isolated mitochondria show pCAG-GFP internalization into this organelle. Furthermore, GFP protein inexpression, mediated by rhodamine carriers, is consistent with the ability displayed by this nanosystem to target mitochondria; due to the different genetic code, fluorescent GFP protein cannot be expressed. Additionally, targeted delivery of pcDNA3-myc-FLNa S2152A and pVAX1-LacZ based vectors to mitochondria has been confirmed by fluorescence confocal microscopy. This work represents a significant step into the development of a mitochondrial therapeutic vector, greatly contributing for advances in the mitochondrial gene therapy field.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Volume 480, 5 September 2015, Pages 287–295
نویسندگان
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