Rhodamine based plasmid DNA nanoparticles for mitochondrial gene therapy

• Gene therapy adds a new perspective of treatment for mitochondrial diseases.
• Biocompatible and size suitable pDNA nanoparticles were produced by co-precipitation.
• These mitochondrial-targeted vectors are able of cell uptake/in vitro transfection.
• p53 Protein inexpression, mediated by this system, shows mitochondria targeting.
• Our strategy has a profound impact in the design of a mitochondrial gene vector.

Conventional treatments for patients suffering from mitochondrial cytopathies are, in most of the cases, inefficient and there is, until now, no effective cure. Mitochondrial gene therapy can be seen as a valuable approach to reestablish normal metabolic function, adding a new perspective of treatment for mitochondrial-related diseases. We developed novel mitochondrial-targeted plasmid DNA nanoparticles by incorporation of rhodamine 123, a fluorescent amphiphile with mitochondria affinity. These nanocarriers have suitable sizes for gene therapy purposes, are biocompatible and are able to protect the encapsulated pDNA from nucleases digestion. Furthermore, the pDNA vectors were easily internalized intodifferent cell linesand targeted delivery to mitochondria was confirmed by fluorescence confocal microscopy. In addition, p53 protein inexpression, mediated by rhodamine nanoparticles, demonstrates the ability of the proposed system to target mitochondria; due to the different genetic code in mitochondria, p53 protein cannot be expressed. Overall, the presented model pDNA constructs possess interesting properties as gene delivery systems and their mitochondrial target ability might have a profound relevance for further engineering of adequate vectors to be applied in mitochondrial gene therapy field.

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