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RNA Technologies and Their Applications pp 29–58Cite as

Selected Strategies for the Delivery of siRNA In Vitro and In Vivo

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Part of the book series: RNA Technologies ((RNATECHN))

Abstract

RNA-based therapeutic strategies are considered as a highly promising alternative to conventional drug development. Among the different classes of oligonucleotide-derived prospective drugs, small interfering RNAs (siRNAs) are of particular interest. However, cellular uptake and subsequent intracellular trafficking to the effector complex (RNA-induced silencing complex; RISC) represent major technical hurdles for the efficacy of these macromolecular drugs. Thus, the development of appropriate delivery systems is an essential requirement to turn these molecules into medicine. In this review, we will focus on two particular auspicious aspects in this context, the phosphorothioate-stimulated uptake of naked siRNA and the use of cell-penetrating peptides as shuttles for a controlled cellular uptake. Moreover, we will present some of the most promising recent approaches for siRNA delivery in vivo, which may help to pave the road to drugs of the future.

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Abbreviations

Ago2:

Argonaute 2

AMD:

age-related macular degeneration

CPP:

cell-penetrating peptide

dsRNA:

double-stranded RNA

ER:

endoplasmic reticulum

exNA:

extracellular nucleic acids

exRNA:

extracellular RNA

GFP:

green fluorescent protein

gp41:

glycoprotein 41

HA:

hemagglutinin

HIV:

human immunodeficiency virus

IL:

interleukin

IFN:

interferon

JEV:

Japanese encephalitis virus

LF2000:

Lipofectamine™ 2000

MEND:

multifunctional envelope-type nano device

miRNA:

microRNA

NLS:

nuclear localization sequence

PCI:

photochemical internalization

PCR:

polymerase chain reaction

PEG:

polyethylene glycol

PEI:

polyethyleneimine

PLL:

Poly-l-Lysine

PS-ON:

phosphorothioate-modified oligonucleotides

PTD:

protein transduction domain

PTGS:

posttranscriptional gene silencing

R8/R9:

oligoarginines

RBD:

RNA-binding domain

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

RVG:

rabies virus glycoprotein

siRNA:

small interfering RNA

shRNA:

short hairpin RNA

ssDNA:

single-stranded DNA

STR-R8:

stearyl-R8

TLR:

Toll-like receptor

TNF:

tumor necrosis factor

TP10:

transportan 10

VEGF:

vascular endothelial growth factor

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Acknowledgments

We apologize to those authors whose work was not cited directly owing to space limitations. T.R. acknowledges funding by EC-grant LSHG-CT-2003-503480.

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  1. Institut für Molekulare Medizin, ZMSZ, Universität zu Lübeck & Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Sandra D. Laufer, Anke Detzer, Georg Sczakiel & Tobias Restle

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  1. Sandra D. Laufer
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  2. Anke Detzer
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  3. Georg Sczakiel
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  4. Tobias Restle
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Correspondence to Sandra D. Laufer .

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  1. Inst. Chemie und Biochemie, FU Berlin, Thielallee 63, Berlin, 14195, Germany

    Volker A. Erdmann

  2. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Laufer, S.D., Detzer, A., Sczakiel, G., Restle, T. (2010). Selected Strategies for the Delivery of siRNA In Vitro and In Vivo . In: Erdmann, V., Barciszewski, J. (eds) RNA Technologies and Their Applications. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12168-5_2

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