Uptake of plasmid/glycosylated polymer complexes and gene transfer efficiency in differentiated airway epithelial cells

Abstract

Glycosylated PEI appears to be a promising gene delivery system since it is more efficient than the sugar-free polymer and does not require endosomolytic agents. However, in differentiated airway gland serous cells, a low gene transfer efficiency was observed that could not be attributed to low expression of membrane lectins or low uptake of glycosylated complexes. An impaired intracellular trafficking of glycosylated complexes in differentiated airway gland serous cells is suggested.

Lactosylated polyethylenimine for gene transfer into airway epithelial cells: role of the sugar moiety in cell delivery and intracellular trafficking of the complexes

“…Indeed, PEI encountered barriers similar to those previously described for viral vectors, that is, a host defence mechanism of mucociliary clearance quite difficult to evade and a low binding and entry into the cells. In order to enhance this last step, we and others have developed PEI substituted with sugar residues to target cell-surface sugar-specific receptors [4][5][6]. Hopefully, the use of glycosylated vectors might also promote an efficient intracellular trafficking and increase the expression of transferred genes by making use of various membrane and soluble sugar receptors that act as shuttles between different cell compartments, including the nucleus (for review, see [7]).…”

“…Hopefully, the use of glycosylated vectors might also promote an efficient intracellular trafficking and increase the expression of transferred genes by making use of various membrane and soluble sugar receptors that act as shuttles between different cell compartments, including the nucleus (for review, see [7]). As we were interested in cystic fibrosis (CF) gene therapy, we have studied the efficiency of various glycosylated PEIs to transfer genes into airway epithelial cells and compared them with the unsubstituted polymer and to other known nonviral vectors such as polylysine and cationic lipids [6]. Among all those vectors, we have identified lactosylated PEI as the most efficient vector in both undifferentiated and differentiated airway cells.…”

Enhancing Effects of Galactosylated Dendrimer/.ALPHA.-Cyclodextrin Conjugates on Gene Transfer Efficiency

“…7,8) Recently, Fajac and co-workers reported that glycosylation of PEI affected intracellular trafficking of its complex with pDNA. 9) Furthermore, some promising findings that glycosyl residues are considered to be very promising candidates of nuclear localization signal have been reported. 10,11) Thus, glycosylation of polymer is one of the effective method to deliver gene to target cells and/or to enhance gene transfer.…”

Gene therapy for cystic fibrosis: an example for lung gene therapy

“…Several groups are modifying polyplexes such as polylysine and polyethylenimine (PEI) by adding sugars, based on the rationale that AECs express lectins, which selectively bind and internalize glycoconjugates. Although glycoconjugates containing lactose have been efficient in cell culture, [40][41][42] their efficacy in vivo remains to be demonstrated.…”