Targeting of cell receptors and gene transfer efficiency: a balancing act.

Abstract:

:Vectors conjugated with ligands recognized by cell surface receptors are of interest for cystic fibrosis gene therapy since these vectors would allow cell-specific targeting. However, an efficient and specific uptake may be abrogated by a subsequent intracellular trafficking leading to an inefficient gene transfer. This has been shown for polylysine substituted with mannose residues. While mannose-specific membrane lectins are predominantly expressed at the surface of airway cells and mannosylated complexes are the most efficiently incorporated glycosylated complexes in these cells, mannosylated complexes lead to a low gene transfer efficiency because of an inefficient exit from endosomal compartments, a high accumulation in lysosomes and an inefficient nuclear import. In contrast, the entry of low amounts of lactosylated complexes is balanced by more efficient intracellular trafficking, leading to an efficient gene transfer. This emphasizes that for a successful gene transfer, it is necessary to find the balance between efficient and specific uptake, and intracellular trafficking that overcomes the various cellular barriers and enables the plasmid to reach the nucleus.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Fajac I,Grosse S,Briand P,Monsigny M

doi

10.1038/sj.gt.3301738

keywords:

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

740-2

issue

11

eissn

0969-7128

issn

1476-5462

journal_volume

9

pub_type

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