Paromomycin and neomycin B derived cationic lipids: synthesis and transfection studies.
Cationic lipid-based nonviral gene delivery is an attractive approach for therapeutic gene transfer. Basically, gene transfection can be achieved by using synthetic vectors that compact DNA, forming cationic lipoplexes which can interact with the cell plasma membrane by electrostatic interactions. Among the basic components of any cationic lipid, the type of cationic headgroup has been shown to have a major role in transfection efficiency. We have previously reported the DNA transfection potential of vectors characterized by a kanamycin A headgroup. The encouraging transfection results obtained with these compounds prompted us to evaluate the potential of cationic lipids bearing headgroups based on other aminoglycosides. Thus, we herein report the synthesis and gene transfection properties of novel cationic lipids consisting of cholesteryl or dioleyl moieties linked, via various spacers, to paromomycin or neomycin B headgroups. Our results confirm that these new aminoglycoside-based cationic lipids are efficient for gene transfection both in vitro and into the mouse airways in vivo. We also investigated physico-chemical properties of the DNA complexes formed by this particular type of synthetic vectors in order to better understand their structure-activity relationships.
INSERM, U915, Nantes F-44000, France.
Mathieu
M
Mével
Matthieu
M
Sainlos
Benoît
B
Chatin
Noufissa
N
Oudrhiri
Michèle
M
Hauchecorne
Olivier
O
Lambert
Jean-Pierre
JP
Vigneron
Pierre
P
Lehn
Bruno
B
Pitard
Jean-Marie
JM
Lehn
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002784:Cholesterol / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D005601:Framycetin / Q000008:administration & dosage* / Q000737:chemistry; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000008:administration & dosage / Q000737:chemistry; D010303:Paromomycin / Q000008:administration & dosage* / Q000737:chemistry; D014162:Transfection / Q000379:methods
D000900:Anti-Bacterial Agents; D009829:Oleic Acids; D049452:Green Fluorescent Proteins; D005601:Framycetin; D010303:Paromomycin; D002784:Cholesterol