Lipidic systems for in vivo siRNA delivery.
The ability of small-interfering RNA (siRNA) to silence specific target genes not only offers a tool to study gene function but also represents a novel approach for the treatment of various human diseases. Its clinical use, however, has been severely hampered by the lack of delivery of these molecules to target cell populations in vivo due to their instability, inefficient cell entry, and poor pharmacokinetic profile. Various delivery vectors including liposomes, polymers, and nanoparticles have thus been developed in order to circumvent these problems. This review presents a comprehensive overview of the barriers and recent progress for both local and systemic delivery of therapeutic siRNA using lipidic vectors. Different strategies for formulating these siRNA-loaded lipid particles as well as the general concern about their safe use in vivo will also be discussed. Finally, current advances in the targeted delivery of siRNA and their impacts on the field of RNA interference (RNAi)-based therapy will be presented.
Wu
Sherry Y
SY
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Level 4, R-Wing, Princess Alexandra Hospital, Ipswich Rd, Buranda, QLD, 4102, Australia.
McMillan
Nigel A J
NA
D000818:Animals; D002412:Cations / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems; D005079:Excipients; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D012449:Safety
D002412:Cations; D005079:Excipients; D008055:Lipids; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D002784:Cholesterol