New synthetic glycolipids for targeted gene transfer: synthesis, formulation in lipoplexes and specific interaction with lectin.
Nonviral gene delivery systems are a promising approach for gene therapy applications, despite their low in vivo gene transfer efficiency. One approach to enhance this efficiency is to incorporate targeting elements into cationic lipid/DNA complexes (lipoplexes). Ligand-containing lipoplexes have to retain their efficiency while exposing accessible ligand on their surface. Physicochemical properties (particle size, surface charge, and efficacy of DNA complexation) of the lipoplexes largely determine their gene transfer efficiency. We synthesized glycolipids with various galactosylated head ligand and incorporated them into lipoplexes. We showed that incorporation of up to 33% mol of glycolipid did not change the physicochemical properties of lipoplexes. Some of our glycolipids yielded lipoplexes whose galactosyl heads were well exposed on the surface as demonstrated by a strong interaction with Ricinus communis agglutinin. Glycolipid-containing lipoplexes gave an efficient gene transfer on hepatocytes, although no ligand-targeted transfection could be observed.
Carrière
Marie
M
ENSCP/CNRS/Gencell S.A., Vitry sur Seine, France.
Escriou
Virginie
V
Jollet
Arnaud
A
Scherman
Daniel
D
Azoulay
Michel
M
Monneret
Claude
C
D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D006017:Glycolipids / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000235:genetics; D006801:Humans; D037102:Lectins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000235:genetics; D008081:Liposomes
D006017:Glycolipids; D037102:Lectins; D008081:Liposomes