HDO has the following strengths:
By linking the ligand to the carrier strand, it is possible to selectively deliver the antisense strand to the diseased site through the binding between this ligand and the receptor expressed on the cell surfaces, so that high efficacy can be obtained.
In the case of HDO, since the ligand is attached to the carrier strand, inhibition of knockdown activity by the antisense strand, which is the active body, is unlikely to occur.
HDO binds to different proteins than single-stranded ASO in the cell, and thus has higher nuclear translocation than ASO. Therefore, it is and advantageous technology for both knockdown and exon skipping.
There is no need to make the linker used for binding the ligand to the carrier strand prone to breaking easily.
The position and the number of ligands bound to the carrier strand can be freely selected.
- HDO may reduce non-specific protein binding, APTT prolongation, and hepatic and renal effects, which are class effects of off-target toxicity*.
* It means hybridization-independent off-target toxicity.