In Vivo RNAi
RiboBio genOFF™ in vivo siRNAs are chemically
modified duplexes intended to use in in
vivo experiments based on its advanced stability, less toxicity, higher
efficiency and easier utility. The new design technologies ensure genOFF™in vivo siRNAs are capable of being constant in serum more than 48
hours, which allows its application in RNAi based drug development, in vivo drug target validation and in vivo gene function investigations.
- Optimized design algorithm minimizes off-target effects
- Chemically modifications improve stability
- Proper conjugates for easily infiltrating into cells
The in vivo RNAi has been used for a variety of
therapeutics validation studies in animal models. However, the highly complexity of in vivo RNAi over in vitro environment hinders its applications. In order to solve this problem, the physical
stability of RNA oligonucleotide and the delivery rate would be two important factors in in vivo settings.
Chemical Modifications Improve Stability
Without chemical modifications, RNA duplex maintians a half-life of less than 10 minutes in 100% human serum. Proper chemical modifications could prolong RNA halif-life and increase stability without biological harmfulness, which in return improves gene silencing performance in vivo. With specific modifications, in vivo genOFF™ RNAi Triggers have been proven obtain longer half-life in serum.
Figure 1. genOFF™ RNAi Triggers in vivo is stabilized against nuclease degradation.
Conjugates Increase the Penetrability
With facilitation of cholesterol that covalently conjugate at the end of RNA oligonucleotide, in vivo genOFF™ RNAi Triggers provide a more efficient entry way into cell. As shown in Figure. 1,in vivo Intra-tumor injection of genOFF™ RNAi Trigger into nude mice effectively reduced tumor growth. Mice injected with Phosphate-buffered saline (PBS) were taken as a control group. One nude mouse from each experimental group was imaged as representatives.
Figure 2. Intra-tumor injection of In vivo genOFF™ RNAi trigger effectively reduced tumor growth
A: PBS control; B: genOFF™ RNAi trigger in vivo.
Fluorescence Labels Tracking Duplexes
With the Cy5 fluorescence labeled at the end of proper position, we can visualize and track the biodistribution of in vivo genOFF™ RNAi Triggers (Cy5) in a more sensitive way.
Figure 3. Visualization of genOFF™ RNAi Trigger in vivo (cy5) effecting activities in mice by intragastrical injection.(Liang, Y. et al., Mol Ther 19(2):381-385, 2011)