1. Technical introduction
(1)HDO Structure
HDO is composed as follows.

Active strand(DNA) : Has a medicinal effect
Carrier strand(RNA) : Transport active strand (medicinal effect) to disease site
Ligand : By binding a substance that specifically binds to a specific receptor to the carrier strand, it transports the active strand to a targeted disease site
(2)HDO's mechanism of action
Step1
The HDO carrier strand (RNA) incorporated into the cell is cleaved by RNase H (enzyme).
Step2
The active strand (DNA) remaining after cleavage binds to the target mRNA.
Step3
When the active strand (DNA) binds to mRNA, it becomes DNA / RNA structure again, and RNase H cleaves the target mRNA.
Step4
As mRNA is cleaved, mRNA expression is suppressed, and drug efficacy is demonstrated.
※RNase H has the property of cleaving RNA among double strands composed of DNA / RNA.

(3)Strengths of HDO technology
HDO has the following strengths:
- By linking the ligand to the carrier strand, it is possible to selectively deliver the active strand to the diseased site, so that high efficacy can be obtained.
- Since HDO adopts a double-stranded structure, HDO is essentially stable, it is possible to avoid toxicity by avoiding chemical modification conventionally applied to the active strand which is a medicinal part
- Since HDO has a double-stranded structure, it becomes a materially stable structure and the enzyme resistance in blood improves
- Since a ligand is bound to a carrier strand having a transporting function, an unexpected medicinal effect due to the ligand (if the ligand is bound to an active strand, the medicinal effect may be remarkably lowered) is unlikely.
- 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
2. Business Introduction
(1)Business model
Rena has the following three business lines.
①Licensing
②Collaborative R&D

③HDO manufacturing
(2)Business lines
①Licensing
This is our business structure for licensing out HDO technology.

②Collaborative R&D
This is our business structure or collaborative R&D with customers, in which Rena designs and provides HDO compounds and moves collaborative R&D forward to find lead HDOs.

③HDO manufacturing
This is our business structure for the HDO manufacturing business in which Rena manufactures, supplies and sells HDOs for target genes only for research and development.
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