Barriers & Carriers for siRNA Delivery                     2/19/2013       1
INTRODUCTION   RNA interference (RNAi): a highly efficient    regulatory process that causes post-transcriptional    gene...
Mechanisms of Gene Silencing by siRNA                      2/19/2013         3
Challenges of siRNA therapy   ‘Off target’ effect: this is the inhibition of gene, the    expression of which should not ...
   most important challenge in the siRNA therapy: issue    of delivery. siRNA, anionic, hydrophilic and unable    to ente...
BARRIERS TO siRNA DELIVERY            Tissue          interstitiu                           Systemic              m       ...
2/19/2013   7
siRNA CARRIERS   Cationic Cell Penetrating Peptides   Polymeric and Dendrimeric Carriers   Lipid-Based Carriers        ...
2/19/2013   9
Recent research work   Delivery of chemo-sensitizing siRNAs to HER2+-    breast cancer cells using RNA aptamers (Kristina...
Reference….   Delivery of siRNA Therapeutics:Barriers and Carriers,    (jie wang et al.The AAPS journal, vol. 12, No.4,  ...
2/19/2013   12
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Barriers and Carriers for Si-RNA Delivery

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Barriers and Carriers for Si-RNA Delivery

  1. 1. Barriers & Carriers for siRNA Delivery 2/19/2013 1
  2. 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. 2/19/2013 2
  3. 3. Mechanisms of Gene Silencing by siRNA 2/19/2013 3
  4. 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. 2/19/2013 4
  5. 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 2/19/2013 5
  6. 6. BARRIERS TO siRNA DELIVERY Tissue interstitiu Systemic m Elimination transportLysosom RES al entrapment BARRIERSdegrada tion Limited internaliza Extravasation tion 2/19/2013 6
  7. 7. 2/19/2013 7
  8. 8. siRNA CARRIERS Cationic Cell Penetrating Peptides Polymeric and Dendrimeric Carriers Lipid-Based Carriers 2/19/2013 8
  9. 9. 2/19/2013 9
  10. 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) 2/19/2013 10
  11. 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) 2/19/2013 11
  12. 12. 2/19/2013 12
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