ORCiD

Nejat Düzgüneş: 0000-0001-6159-1391

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.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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