Drug Delivery System

Drug Delivery System

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 systemsMechanismsTypical Examples
Lipophilic siRNA derivatesEPR, increased circulation half-life, receptor-mediated endocytosis, pH-induced lipid ionization and membrane disruption, peptide-induced membrane fusionCholesterol-siRNA, lipid-based nanoparticles (LPNs)
siRNA-receptor ligandReceptor-mediated endocytosis, systemic circulation via subcutaneous injectionGalNAc-siRNA
siRNA-antibodyReceptor-mediated endocytosis, long circulation half-life mediated by Fc domain, release of payload by catabolism of antibodyTHIOMAB-siRNA
siRNA-aptamerReceptor-mediated endocytosisCCR5 aptamer– DsiRNA, gp120 aptamer–DsiRNA
siRNA-cpG oligonucleotideTLR9 binding to CpG (immune-stimulatory), nonspecific uptake via gymnosisCpG(A)–STAT3 siRNA
siRNA-peptideTargeted or non-targeted uptake, enhanced endosomal escapePenetratin–siRNA
Dynamic polyconjugate of siRNATargeted or non-targeted uptake, enhanced endosomal escapepolyarginine– siRNA
ExosomesIncreased circulation half-life via CD47 expression, receptor-mediated uptakeExosome delivery of KRAS siRNA, exosome delivery to CNS

Figure 1. A scheme of siRNA bioconjugates Figure 1. A scheme of siRNA bioconjugates

We can provide the following RNA drug delivery system for your drug development

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.
* Only for research. Not suitable for any diagnostic or therapeutic use.
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