TY - JOUR
T1 - Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: Novel options by phosphorothioate-stimulated delivery
AU - Mescalchin, Alessandra
AU - Detzer, Anke
AU - Wecke, Maria
AU - Overhoff, Marita
AU - Wünsche, Winfried
AU - Sczakiel, Georg
PY - 2007/10/1
Y1 - 2007/10/1
N2 - The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.
AB - The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.
UR - http://www.scopus.com/inward/record.url?scp=35348861314&partnerID=8YFLogxK
U2 - 10.1517/14712598.7.10.1531
DO - 10.1517/14712598.7.10.1531
M3 - Scientific review articles
C2 - 17916045
AN - SCOPUS:35348861314
SN - 1471-2598
VL - 7
SP - 1531
EP - 1538
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 10
ER -
