Synthesis of chemically modified siRNA
siRNA is unstable in vivo, easily degraded by nucleases, and easily cleared by the kidneys with a short half-life. At the same time, exogenous nucleic acid molecules have immunogenicity, which can easily cause immune reactions in the human body. In order to improve the stability, specificity, and delivery efficiency of siRNA, researchers have developed various chemical modification strategies. These modifications can protect siRNA from degradation, reduce immune response, and enhance its bioavailability in vivo. Biosyntech can provide conventional chemically modified siRNA products, as well as various customized modified siRNA products. The common types of modifications are as follows:
Phosphonate modification:
Ribose modification:
Base modification:
The chemical modification effect is as follows:
No. | Modification | Function |
1 | phosphorothioate(P=S) | Increase siRNA stability, antisense ability, and improve intracellular delivery efficiency |
2 | chemical modification(2'-OMe) | Improve siRNA stability and enhance resistance to RNase |
3 | chemical modification(2'-F) | Improve siRNA stability and enhance resistance to RNase |
4 | chemical modification(2'-MOE) | Improve siRNA stability and reduce non-specific immune responses |
6 | chemical modification(5'VinylPhosphonate ) | Resist degradation by nucleases and enhance in vivo silencing effect |
7 | chemical modification(LNA) | Improve affinity for targets and serum stability |
8 | chemical modification(GNA) | Improve the thermal stability of siRNA and reduce off target effects |
9 | chemical modification(UNA) | Promote the loading of siRNA antisense chains instead of sense chains into RISC complexes and enhance siRNA nuclease resistance |
10 | Phosphorylation modification(Phosphate) | Provide siRNA activity to promote siRNA recognition of target gene |
11 | GalNAc modification | Realize specific delivery of siRNA targeting the liver |
12 | Lipid modification | Specific delivery of siRNA (such as CNS) |
Biosyntech can also design siRNA modification strategies according to customer requirements. The following are several common publicly available modification methods:
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