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Full-Text Articles in Medicine and Health Sciences
Mechanisms Of Gene Transfer Mediated By Lipoplexes Associated With Targeting Ligands Or Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Mechanisms Of Gene Transfer Mediated By Lipoplexes Associated With Targeting Ligands Or Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
All Dugoni School of Dentistry Faculty Articles
Association of a targeting ligand such as transferrin, or an endosome disrupting peptide such as GALA, with cationic liposome-DNA complexes ('lipoplexes') results in a significant enhancement of transfection of several cell types. Although these strategies can overcome some of the barriers to gene delivery by lipoplexes, the mechanisms by which they actually enhance transfection is not known. In studies designed to establish the targeting specificity of transferrin, we found that apo-transferrin enhances transfection to the same extent as transferrin, indicating that internalization of the lipoplexes is mostly independent of transferrin receptors. These observations were reinforced by results obtained from competitive …
Transfection Of Human Macrophages By Lipoplexes Via The Combined Use Of Transferrin And Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Elizabeth Pretzer, Paul Dazin, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Transfection Of Human Macrophages By Lipoplexes Via The Combined Use Of Transferrin And Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Elizabeth Pretzer, Paul Dazin, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
All Dugoni School of Dentistry Faculty Articles
The crucial function of macrophages in a variety of biological processes and pathologies render these cells important targets for gene therapeutic interventions. Commonly used synthetic gene delivery vectors have not been successful in transfecting these non-dividing cells. A combination strategy involving cationic liposomes to condense and carry DNA, transferrin to facilitate cellular uptake, and the pH-sensitive peptide GALA to promote endosome destabilization, resulted in significant expression of a luciferase gene. Transfection of macrophages was dependent on the degree of differentiation of the cells. The quaternary complexes of cationic liposomes, DNA, transferrin, and GALA exhibited a net negative charge, which may …