2. INTRODUCTION
RNA interference (RNAi): a highly efficient
regulatory process that causes post-transcriptional
gene silencing in most eukaryotic cells.
The mechanisms of RNAi were first reported in
Caenorhabditis elegans.
promising new approach for producing gene-specific
inhibition and knockouts, producing transgenic
animal models, and designing new therapeutics.
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4. Challenges of siRNA therapy
‘Off target’ effect: this is the inhibition of gene, the
expression of which should not be targeted because
this gene shared partial homology with the siRNA, so
the inadvertent silencing of non target gene may lead
to potential toxicity.
Immune stimulation: this is recognition of an siRNA
by innate immune system, and immune system
activation via dsRNA sensor.
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5. most important challenge in the siRNA therapy: issue
of delivery. siRNA, anionic, hydrophilic and unable
to enter the cell by passive diffusion mechanism.
In vivo administration of naked siRNA into
appropriate disease sites, it rapidly degrade by
enzymes, and rapidly renal elimination, limited
penetration across the capillary endothelium and
insufficient uptake by tissue cells
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6. BARRIERS TO siRNA DELIVERY
Tissue
interstitiu Systemic
m Elimination
transport
Lysosom RES
al entrapment
BARRIERS
degrada
tion
Limited
internaliza
Extravasation
tion
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10. Recent research work
Delivery of chemo-sensitizing siRNAs to HER2+-
breast cancer cells using RNA aptamers (Kristina W.
Thiel1 et al.,Nucleic Acids Research, 2012, 1–19)
Delivery of sirna into breast cancer cells via phage
fusion protein-targeted liposomes (deepa bedi et al.,
Nanomedicine. 2011 June ; 7(3): 315–323)
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11. Reference….
Delivery of siRNA Therapeutics:Barriers and Carriers,
(jie wang et al.The AAPS journal, vol. 12, No.4,
December 2010)
siRNA delivery system for cancer treatment,(yu-kyoung
oh et al.Advance Drug delivery reviews 61(2009) 850-
862)
Delivery of chemo-sensitizing siRNAs to HER2+-breast
cancer cells using RNA aptamers (Kristina W. Thiel1 et
al.,Nucleic Acids Research, 2012, 1–19)
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