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sirna delivery

sirna delivery

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sirna delivery

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  1. Drug Delivery System Exosome Liposomes GalNAc-siRNA Conjugates Antibody-siRNA Conjugates Peptide-siRNA conjugates Polymer-siRNA Conjugates Cholesterol-siRNA Conjugates Nanoparticle-siRNA Conjugates Naked RNA drugs will degrade rapidly as there are a large number of RNases in the blood, it will affect the drug efficacy of RNAi. Therefore, it's very important to improve the stability of naked RNA. Except for chemically modification, researchers are working hard on siRNA drug delivery system nowadays. Drug delivery system is becoming an important tool for delivering the candidate siRNA drugs to target cells. In August 2018, the US FDA approved the first siRNA drug, called ONPATTRO™ (Patisiran) by Alnylam Pharmaceuticals, for the treatment of hereditary transthyretin polyneuropathy. This was an important milestone for the field of siRNA drugs and opens the door for the research of other siRNA drug delivery system. Here are the delivery systems and their mechanisms and some typical examples. Delivery systems Mechanisms Typical Examples EPR, increased circulation half-life, receptor-mediated endocytosis, pH-induced lipid ionization and membrane disruption, peptide-induced membrane fusion Lipophilic siRNA derivates Cholesterol-siRNA, lipid-based nanoparticles (LPNs) Receptor-mediated endocytosis, systemic circulation via subcutaneous injection siRNA-receptor ligand GalNAc-siRNA Receptor-mediated endocytosis, long circulation half-life mediated by Fc domain, release of payload by catabolism of antibody siRNA-antibody THIOMAB-siRNA

  2. CCR5 aptamer– DsiRNA, gp120 aptamer–DsiRNA siRNA-aptamer Receptor-mediated endocytosis siRNA-cpG oligonucleotide TLR9 binding to CpG (immune-stimulatory), nonspecific uptake via gymnosis CpG(A)–STAT3 siRNA siRNA-peptide Targeted or non-targeted uptake, enhanced endosomal escape Penetratin–siRNA Dynamic polyconjugate of siRNA Targeted or non-targeted uptake, enhanced endosomal escape polyarginine– siRNA Exosome delivery of KRAS siRNA, exosome delivery to CNS Increased circulation half-life via CD47 expression, receptor-mediated uptake Exosomes

  3. Figure 1. A scheme of siRNA bioconjugates We can provide the following RNA drug delivery system for your drug development Exosomes Liposomes Cholesterol-siRNA conjugates nanoparticle-siRNA conjugates GalNAc-siRNA conjugates Antibody-siRNA conjugates Peptide-siRNA conjugates polymer-siRNA conjugates         Ref: 1.Dong, Y., Siegwart, D. J., & Anderson, D. G. (2019). Strategies, design, and chemistry in siRNA delivery systems. Advanced Drug Delivery Reviews. 2.Chernikov IV, Vlassov VV and Chernolovskaya EL(2019) Current development of siRNA bioconjugates: from research to the clinic. Front. Pharmacol. 10:444. https://rna.bocsci.com/products-services/drug-delivery-system.html