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Combined transductional and transcriptional targeting of melanoma cells by artificial virus‐like particles
Author(s) -
Nahde Thomas,
Müller Kristina,
Fahr Alfred,
Müller Rolf,
Brüsselbach Sabine
Publication year - 2001
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.203
Subject(s) - transduction (biophysics) , transfection , melanoma , transgene , biology , green fluorescent protein , reporter gene , viral vector , microbiology and biotechnology , luciferase , cell culture , chemistry , cancer research , gene , gene expression , biochemistry , recombinant dna , genetics
Background Artificial virus‐like particles (AVPs) represent a novel type of liposomal vector resembling retroviral envelopes. AVPs are serum‐resistant and non‐toxic and can be endowed with a peptide ligand as a targeting device. The vitronectin receptor, α v β 3 ‐integrin, is commonly upregulated on malignant melanoma cells. In the present study we investigated whether AVPs carrying cyclic peptides with an RGD integrin binding motif (RGD‐AVPs) are suitable for the specific and efficient transduction of human melanoma cells. Methods Plasmid DNA was complexed with low molecular weight non‐linear polyethyleneimine and packaged into anionic liposomes. Transduction efficiencies were determined after transient transfection of different cell lines in serum‐free medium using green fluorescent protein or luciferase reporter genes. Results We demonstrated that RGD‐AVPs transduced human melanoma cells with high efficiencies of >60%. Efficient transduction was clearly dependent on the presence of the cyclic RGD ligand and was selective for melanoma cells. The specificity of the vector system could be further enhanced by using the melanocyte‐specific tyrosinase promoter to drive transgene expression. Conclusion Our findings suggest that the AVP technology is a useful approach for generating highly efficient and specific non‐viral vectors for melanoma targeting, in particular in a setting of combined transductional and transcriptional targeting. Copyright © 2001 John Wiley & Sons, Ltd.