Efficient nucleic acid transduction with lipoplexes containing novel piperazine- and polyamine-conjugated cholesterol derivatives.
To advance the use of cationic lipids for non-viral nucleic acid vector formulation, a panel of novel nitrogen heterocycle cholesteryl derivatives containing a biodegradable carbamate linker was synthesised. Optimally acting piperazine and cyclen compounds had nucleic acid-binding and lipoplex nanoparticle formation properties that were suitable for their use as non-viral vectors. It was found that the lipoplexes formed were capable of efficient non-toxic nucleic acid delivery to cells in culture. The chemical structure of individual cationic lipids, which is likely to influence lipoplex formation, affected efficiency of DNA or RNA transfection. The results indicated that the cyclen containing compound possessing two cholesteryl moieties resulted in efficient siRNA-mediated target gene silencing but was a poor reagent for DNA transfection.
Islam
Rafique Ul
RU
Department of Molecular Medicine and Haematology, Antiviral Gene Therapy Research Unit, University of the Witwatersrand Medical School, Private Bag 3, WITS, South Africa.
Hean
Justin
J
van Otterlo
Willem A L
WA
de Koning
Charles B
CB
Arbuthnot
Patrick
P
D000818:Animals; D002412:Cations; D002477:Cells / Q000378:metabolism; D002788:Cholesterol Esters / Q000737:chemistry*; D000080027:Cyclams; D004247:DNA / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D012313:RNA / Q000493:pharmacokinetics; D034741:RNA, Small Interfering / Q000493:pharmacokinetics; D014161:Transduction, Genetic / Q000379:methods*
D002412:Cations; D002788:Cholesterol Esters; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008055:Lipids; D010879:Piperazines; D011073:Polyamines; D034741:RNA, Small Interfering; D012313:RNA; D004247:DNA; C038072:cyclen