| Literature DB >> 18438401 |
Akin Akinc1, Andreas Zumbuehl, Michael Goldberg, Elizaveta S Leshchiner, Valentina Busini, Naushad Hossain, Sergio A Bacallado, David N Nguyen, Jason Fuller, Rene Alvarez, Anna Borodovsky, Todd Borland, Rainer Constien, Antonin de Fougerolles, J Robert Dorkin, K Narayanannair Jayaprakash, Muthusamy Jayaraman, Matthias John, Victor Koteliansky, Muthiah Manoharan, Lubomir Nechev, June Qin, Timothy Racie, Denitza Raitcheva, Kallanthottathil G Rajeev, Dinah W Y Sah, Jürgen Soutschek, Ivanka Toudjarska, Hans-Peter Vornlocher, Tracy S Zimmermann, Robert Langer, Daniel G Anderson.
Abstract
The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2'-O-methyl (2'-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.Entities:
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Year: 2008 PMID： 18438401 PMCID： PMC3014085 DOI： 10.1038/nbt1402
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908