Source:http://linkedlifedata.com/resource/pubmed/id/10637443
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2000-2-24
|
| pubmed:abstractText |
Peptide nucleic acids (PNAs) are synthetic polynucleobase molecules, which bind to DNA and RNA with high affinity and specificity. Although PNAs have enormous potential as anti-sense agents, the success of PNA-mediated gene therapy will require efficient cellular uptake and sub-cellular trafficking. At present these mechanisms are poorly understood. To address this, we have studied the uptake of biotinylated PNAs into cultured cell lines using fluorescence confocal microscopy. In human myoblasts, initial punctate staining was followed by the release of PNAs into the cytosol and subsequent localisation and concentration in the nucleus. To determine whether PNAs could also be used as therapeutic agents for mtDNA disease, we attempted to localise PNAs to the mitochondrial matrix. When attached to the presequence peptide of the nuclear-encoded human cytochrome c oxidase (COX) subunit VIII, the biotinylated PNA was successfully imported into isolated organelles in vitro. Furthermore, delivery of the biotinylated peptide-PNA to mitochondria in intact cells was confirmed by confocal microscopy. These studies demonstrate that biotinylated PNAs can be directed across cell membranes and to a specific sub-cellular compartment within human cells - highlighting the importance of these novel molecules for human gene therapy.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0969-7128
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
6
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1919-28
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| pubmed:dateRevised |
2009-9-29
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| pubmed:meshHeading |
pubmed-meshheading:10637443-Animals,
pubmed-meshheading:10637443-Biotinylation,
pubmed-meshheading:10637443-Cell Line,
pubmed-meshheading:10637443-Cell Nucleus,
pubmed-meshheading:10637443-Cytosol,
pubmed-meshheading:10637443-Electron Transport Complex IV,
pubmed-meshheading:10637443-Gene Transfer Techniques,
pubmed-meshheading:10637443-Genetic Engineering,
pubmed-meshheading:10637443-Genetic Vectors,
pubmed-meshheading:10637443-Humans,
pubmed-meshheading:10637443-Image Processing, Computer-Assisted,
pubmed-meshheading:10637443-Microscopy, Confocal,
pubmed-meshheading:10637443-Mitochondria, Heart,
pubmed-meshheading:10637443-Mitochondria, Liver,
pubmed-meshheading:10637443-Mitochondrial Myopathies,
pubmed-meshheading:10637443-Myocardium,
pubmed-meshheading:10637443-Peptide Nucleic Acids,
pubmed-meshheading:10637443-Rats
|
| pubmed:year |
1999
|
| pubmed:articleTitle |
Peptide nucleic acid delivery to human mitochondria.
|
| pubmed:affiliation |
Department of Neurology, The University of Newcastle upon Tyne, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|