TY - JOUR
T1 - Phosphorothioate-stimulated uptake of siRNA by mammalian cells: A novel route for delivery
AU - Detzer, Anke
AU - Sczakiel, Georg
PY - 2009/12/1
Y1 - 2009/12/1
N2 - The efficient delivery of biologically functional short interfering RNA (siRNA) in vivo remains a widely unresolved technical problem in therapeutic drug development. The repertoire of concepts for the cellular uptake of oligonucleotide-based tools and drugs has been extended by the mechanistically novel finding that phosphorothioate (PS)-modified single-stranded oligodeoxyribonucleotides (ON) promote the intracellular accumulation of naked extra-cellular siRNA in a variety of cell types. This mode of delivery gives rise to substantial intracellular amounts of siRNA, up to 104 siRNA molecules per cell. Conversely, the moderate biological effectiveness strongly indicates that intracellular release of siRNA from sub-cellular compartments where it seems to be trapped is a necessary step towards efficient target suppression. Here, we summarize key characteristics of the PS-stimulated cellular uptake of siRNA and describe concepts for the increase of intracellular delivery of biologically functional siRNA.
AB - The efficient delivery of biologically functional short interfering RNA (siRNA) in vivo remains a widely unresolved technical problem in therapeutic drug development. The repertoire of concepts for the cellular uptake of oligonucleotide-based tools and drugs has been extended by the mechanistically novel finding that phosphorothioate (PS)-modified single-stranded oligodeoxyribonucleotides (ON) promote the intracellular accumulation of naked extra-cellular siRNA in a variety of cell types. This mode of delivery gives rise to substantial intracellular amounts of siRNA, up to 104 siRNA molecules per cell. Conversely, the moderate biological effectiveness strongly indicates that intracellular release of siRNA from sub-cellular compartments where it seems to be trapped is a necessary step towards efficient target suppression. Here, we summarize key characteristics of the PS-stimulated cellular uptake of siRNA and describe concepts for the increase of intracellular delivery of biologically functional siRNA.
UR - http://www.scopus.com/inward/record.url?scp=74049105646&partnerID=8YFLogxK
U2 - 10.2174/156802609789630884
DO - 10.2174/156802609789630884
M3 - Scientific review articles
C2 - 19860711
AN - SCOPUS:74049105646
SN - 1568-0266
VL - 9
SP - 1109
EP - 1116
JO - Current Topics in Medicinal Chemistry
JF - Current Topics in Medicinal Chemistry
IS - 12
ER -
