title: Comparison of nanocomplexes with branched and linear peptides for siRNA delivery.
abstract: Efficient delivery of small interfering RNA (siRNA) remains the greatest technological barrier to the clinical implementation of RNA interference strategies. We are investigating the relationship between the biophysical properties of siRNA nanocomplexes and their transfection efficiency as an approach to the generation of improved formulations. Peptide-based formulations are of great interest, and so in this study we have compared nanocomplex formulations for siRNA delivery containing linear and branched oligolysine or oligoarginine peptides. Peptides were combined with cationic liposomes in siRNA formulations and compared for transfection efficiency, siRNA packaging efficiency, biophysical properties, and particle stability. Nanocomplexes containing linear peptides were more condensed and stable than branched peptide formulations; however, their silencing activity was lower, suggesting that their greater stability might limit siRNA release within the cell. Thus, differences in transfection appeared to be associated with differences in packaging and stability, indicating the importance of optimizing this feature in siRNA nanocomplexes.
authors: Wolfson Centre for Gene Therapy of Childhood Disease, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
authors: Aristides D
authors: AD
authors: Tagalakis
authors: Luisa
authors: L
authors: Saraiva
authors: David
authors: D
authors: McCarthy
authors: Kenth T
authors: KT
authors: Gustafsson
authors: Stephen L
authors: SL
authors: Hart
mesh_terms: D000818:Animals; D002412:Cations; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D008081:Liposomes; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
chemical_list: D002412:Cations; D008081:Liposomes; D010455:Peptides; D034741:RNA, Small Interfering; D008156:Luciferases