The benefit of hydrophobic domain asymmetry on the efficacy of transfection as measured by in vivo imaging.
We, and others, have observed that the structure of cationic lipids appears to have a significant effect on the transfection efficacy of optimized nucleic acid/cationic lipid complexes (lipoplexes) used for in vitro and in vivo gene delivery and expression. Although there are many in vitro comparisons of lipid reagents for gene delivery, few comparisons have been made in vivo. We previously reported the effects of changes in hydrophobic domain chain length and chain asymmetry, changes in headgroup composition, and counterion exchange. We have observed in our own work over many years the apparent superiority of asymmetric versus symmetric hydrocarbon domains for otherwise similar lipids. In this investigation we use in vivo whole animal brain imaging to evaluate the contribution of symmetric versus asymmetric hydrophobic domains on what we previously determined to be optimal chain lengths for in vitro transfections. We specifically investigated several glycerol-based lipids; however, the rare reports of asymmetric non-glycerol-based lipids also support our observations. We found that asymmetric, two-chain cationic lipids of 14 to 18 carbons perform significantly better in vivo, as analyzed by whole animal imaging, than the paired symmetric lipids.
Department of Anesthesia and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6112, USA.
Michael H
MH
Nantz
Christopher W
CW
Dicus
Brendan
B
Hilliard
Sri
S
Yellayi
Shaomin
S
Zou
James G
JG
Hecker
D000818:Animals; D001921:Brain / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009696:Nucleic Acids / Q000737:chemistry; D014162:Transfection
D008055:Lipids; D009696:Nucleic Acids