ORCiD
Nejat Düzgüneş: 0000-0001-6159-1391
Department
Biomedical Sciences
Document Type
Article
Publication Title
Gene Therapy
ISSN
0969-7128
Volume
6
Issue
11
DOI
10.1038/sj.gt.3301015
First Page
1798
Last Page
1807
Publication Date
11-1-1999
Abstract
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 inhibition studies either by preincubating the cells with an excess of free ligand or with various 'receptor-blocking' lipoplexes. Transfection of cells in the presence of drugs that interfere with the endocytotic pathway provided additional insights into the mechanisms of gene delivery by transferrin- or GALA-lipoplexes. Our results indicate that transferrin-lipoplexes deliver transgenes by endocytosis primarily via a non-receptor-mediated mechanism, and that acidification of the endosomes is partially involved in this process.
Recommended Citation
Simões, S.,
Slepushkin, V.,
Pires, P.,
Gaspar, R.,
Pedroso De Lima, M. C.,
&
Düzgüneş, N.
(1999).
Mechanisms of gene transfer mediated by lipoplexes associated with targeting ligands or pH-sensitive peptides.
Gene Therapy, 6(11), 1798–1807.
DOI: 10.1038/sj.gt.3301015
https://scholarlycommons.pacific.edu/dugoni-facarticles/629
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This work is licensed under a Creative Commons Attribution 4.0 International License.
