An approach to transgene expression in liver endothelial cells using a liposome-based gene vector coated with hyaluronic acid

Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells

“…We quantitatively compared the cellular uptake of HA (600 negatively charged cell membranes, is consistent with previously reported findings [14].…”

“…In the preparation, HA coats the carrier surface, when the R8/GALA-MEND and HA are simply mixed with one another. The coating is held in place via electrostatic interactions and does not involve PEGylation, since PEGylation typically results in a decrease in the transfection activity of the carrier, as previously reported [14]. An HA-R8/GALA-MEND prepared using HAs with different molecular weights (600 kDa or 80 kDa) was investigated in terms of the physicochemical properties ( Figure 2 and Table 1).…”

“…The R8/GALA-MEND was prepared by the lipid film hydration method, as previously reported [9,14]. First, pDNA was condensed with polycations to form condensed pDNA particles.…”

“…More recently, we developed a dual-ligand positively charged R8-MEND that was modified with negatively charged hyaluronic acid (HA) via electrostatic interactions but not with PEG [14]. HA is a natural ligand for cancer cells and liver endothelial cells overexpressing CD44, thus it would be expected that HA would be a specific ligand for / targeted to cancer and liver endothelial cells.…”

Progresses towards safe and efficient gene therapy vectors

“…These can range from natural ligands to peptides and antibodies (reviewed in [ 7 ]). For example, liposome-based vectors have been functionalized with hyaluronic acid (HA) to specifically transduce endothelial liver cells, because these cells express HA receptors [ 31 ]. Antigen-presenting cells have been shown to be efficiently transduced using a “mannosylated” PEI-based vector [ 32 ].…”