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Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Nature Biotechnology 33, 870 (2015). doi:10.1038/nbt.3298 Authors: Anders Wittrup, Angela Ai, Xing Liu, Peter Hamar, Radiana Trifonova, Klaus Charisse, Muthiah Manoharan, Tomas Kirchhausen & Judy Lieberman A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient process, we studied the uptake and cytosolic release of siRNAs, formulated in lipoplexes or lipid n...
Source: Nature Biotechnology - July 20, 2015 Category: Biotechnology Authors: Anders WittrupAngela AiXing LiuPeter HamarRadiana TrifonovaKlaus CharisseMuthiah ManoharanTomas KirchhausenJudy Lieberman Tags: Research Source Type: research

Corrigendum: Taking charge of siRNA delivery
Nature Biotechnology 33, 563 (2015). doi:10.1038/nbt0515-563c Authors: Anastasia Khvorova, Maire F Osborn & Matthew R Hassler
Source: Nature Biotechnology - May 12, 2015 Category: Biotechnology Authors: Anastasia KhvorovaMaire F OsbornMatthew R Hassler Tags: Research Source Type: research

Taking charge of siRNA delivery
Nature Biotechnology 32, 1197 (2014). doi:10.1038/nbt.3091 Authors: Anastasia Khvorova, Maire F Osborn & Matthew R Hassler Delivery of siRNA into cells is achieved by neutralizing the negative charge of the phosphate backbone in a reversible manner.
Source: Nature Biotechnology - December 9, 2014 Category: Biotechnology Authors: Anastasia KhvorovaMaire F OsbornMatthew R Hassler Tags: News and Views Source Type: research

Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications
Nature Biotechnology 32, 1256 (2014). doi:10.1038/nbt.3078 Authors: Bryan R Meade, Khirud Gogoi, Alexander S Hamil, Caroline Palm-Apergi, Arjen van den Berg, Jonathan C Hagopian, Aaron D Springer, Akiko Eguchi, Apollo D Kacsinta, Connor F Dowdy, Asaf Presente, Peter Lönn, Manuel Kaulich, Naohisa Yoshioka, Edwige Gros, Xian-Shu Cui & Steven F Dowdy RNA interference (RNAi) has great potential to treat human disease. However, in vivo delivery of short interfering RNAs (siRNAs), which are negatively charged double-stranded RNA macromolecules, remains a major hurdle. Current siRNA delivery has begun to move awa...
Source: Nature Biotechnology - November 17, 2014 Category: Biotechnology Authors: Bryan R MeadeKhirud GogoiAlexander S HamilCaroline Palm-ApergiArjen van den BergJonathan C HagopianAaron D SpringerAkiko EguchiApollo D KacsintaConnor F DowdyAsaf PresentePeter LönnManuel KaulichNaohisa YoshiokaEdwige GrosXian-Shu CuiSteven F Dowdy Tags: Research Source Type: research

A window onto siRNA delivery
Nature Biotechnology 31, 611 (2013). doi:10.1038/nbt.2634 Authors: Yuhua Wang & Leaf Huang Two studies trace the intracellular trafficking of siRNA delivered by lipid nanoparticles.
Source: Nature Biotechnology - July 9, 2013 Category: Biotechnology Authors: Yuhua WangLeaf Huang Tags: News and Views Source Type: research

Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape
Nature Biotechnology 31, 638 (2013). doi:10.1038/nbt.2612 Authors: Jerome Gilleron, William Querbes, Anja Zeigerer, Anna Borodovsky, Giovanni Marsico, Undine Schubert, Kevin Manygoats, Sarah Seifert, Cordula Andree, Martin Stöter, Hila Epstein-Barash, Ligang Zhang, Victor Koteliansky, Kevin Fitzgerald, Eugenio Fava, Marc Bickle, Yannis Kalaidzidis, Akin Akinc, Martin Maier & Marino Zerial
Source: Nature Biotechnology - June 23, 2013 Category: Biotechnology Authors: Jerome GilleronWilliam QuerbesAnja ZeigererAnna BorodovskyGiovanni MarsicoUndine SchubertKevin ManygoatsSarah SeifertCordula AndreeMartin StöterHila Epstein-BarashLigang ZhangVictor KotelianskyKevin FitzgeraldEugenio FavaMarc BickleYannis KalaidzidisAkin Tags: Research Source Type: research

Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling
Nature Biotechnology 31, 653 (2013). doi:10.1038/nbt.2614 Authors: Gaurav Sahay, William Querbes, Christopher Alabi, Ahmed Eltoukhy, Sovan Sarkar, Christopher Zurenko, Emmanouil Karagiannis, Kevin Love, Delai Chen, Roberto Zoncu, Yosef Buganim, Avi Schroeder, Robert Langer & Daniel G Anderson Despite efforts to understand the interactions between nanoparticles and cells, the cellular processes that determine the efficiency of intracellular drug delivery remain unclear. Here we examine cellular uptake of short interfering RNA (siRNA) delivered in lipid nanoparticles (LNPs) using cellular trafficking probes in co...
Source: Nature Biotechnology - June 23, 2013 Category: Biotechnology Authors: Gaurav SahayWilliam QuerbesChristopher AlabiAhmed EltoukhySovan SarkarChristopher ZurenkoEmmanouil KaragiannisKevin LoveDelai ChenRoberto ZoncuYosef BuganimAvi SchroederRobert LangerDaniel G Anderson Tags: Research Source Type: research

Efficient and specific gene knockdown by small interfering RNAs produced in bacteria
Nature Biotechnology 31, 350 (2013). doi:10.1038/nbt.2537 Authors: Linfeng Huang, Jingmin Jin, Padraig Deighan, Evgeny Kiner, Larry McReynolds & Judy Lieberman Synthetic small interfering RNAs (siRNAs) are an indispensable tool to investigate gene function in eukaryotic cells and may be used for therapeutic purposes to knock down genes implicated in disease. Thus far, most synthetic siRNAs have been produced by chemical synthesis. Here we present a method to produce highly potent siRNAs in Escherichia coli. This method relies on ectopic expression of p19, an siRNA-binding protein found in a plant RNA virus. Whe...
Source: Nature Biotechnology - March 10, 2013 Category: Biotechnology Authors: Linfeng HuangJingmin JinPadraig DeighanEvgeny KinerLarry McReynoldsJudy Lieberman Tags: Research Source Type: research