Novel branching membrane translocational peptide as gene delivery vector.
A fragment of HIV-tat protein, RKKRRQRRR, has been shown to have membrane penetration and nuclear localization properties, which are critical attributes of gene therapy agents. In this study, we designed a series of arborizing tat peptides, containing 1-8 tat moieties, and evaluated them as transfection enhancers in a variety of cell lines. We found that all compounds complexed with plasmid DNA, but only the molecule containing 8 tat-peptide chains shows significant transfection capabilities. Using rhodamine labeled plasmid and eight tat-peptide complex, we were also able to demonstrate intracellular delivery of the complex by fluorescence microscopy.
Tung
Ching-Hsuan
CH
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. tung@helix.mgh.harvard.edu
Mueller
Stephanie
S
Weissleder
Ralph
R
D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D051379:Mice; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D014162:Transfection
D015696:Gene Products, tat; D010446:Peptide Fragments; D004247:DNA