title: Synthetic SiRNA Delivery: Progress and Prospects.
abstract: Small interfering RNA (siRNA) is a powerful tool for modulating gene expression by RNA interference (RNAi). Duplex RNA oligonucleotides induce cleavage of homologous target transcripts, thereby enabling posttranscriptional silencing of potentially any gene. As such, siRNAs may have utility as novel pharmaceuticals for a wide range of diseases. However, a lack of "drug-likeness," physiological barriers, and potential toxicities have meant that systemic delivery of SiRNAs in vivo remains a major challenge. Here we discuss various strategies that have been employed to solve the problem of SiRNA delivery. These include chemical modification of the SiRNA, direct conjugation to bioactive moieties, and nanoparticle formulations.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.|Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.|Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Roberts
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
authors.forename: Kariem
authors.initials: K
authors.lastname: Ezzat
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.|Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Samir
authors.initials: S
authors.lastname: El Andaloussi
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA. marc.weinberg@wits.ac.za.|Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Johannesburg, WITS 2050, South Africa. marc.weinberg@wits.ac.za.|HIV Pathogenesis Research Unit, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Johannesburg, WITS 2050, South Africa. marc.weinberg@wits.ac.za.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering
keywords: Cell-penetrating peptides; Lipid nanoparticles; Lipidoids; SiRNA conjugates; SiRNA delivery