Ribozyme and omics

Anti-cancer development based on RNA Platform technology Core competence to meet diverse unmet medical needs

Targeted Gene / Advantage of Technology

Telomerase – Targeted molecule for liver cancer treatment

  • Ribonucleoprotein enzyme that maintains the protective telomere structures (telomeric repeat (TTAGGG)) in eukaryotic chromosome
  • hTR (RNA component) + hTERT (reverse transcriptase)
  • Expression level of hTERT relates with telomerase activity
  • Selective expression in highly proliferative cells (bone marrow stem cells, germ cells…) and 90% or more of cancer cells - Activated in most stages of liver cancer
  • Regulation of gene expression involved in cancer cell growth & progression
  • Activated in the majority of HCCs, most frequently with TERT promoter mutation, although variable among HCC (Nat. Commun. 2013)
  • TERT overexpression is significant prognostic factor for late IHR in HCC treated with curative resection and survival duration (Sci. Rep. 2017)

hTERT: Useful targeted molecule for developing liver cancer therapies

Limitations of existing cancer therapy approaches via targeting telomerase

01
Long lag period before telomere shortening sufficient for cellular senescence
02
Resistance to telomerase inhibitors
03
Alternative mechanism of telomere maintenance
04
Increase in malignancy by genomic instability
05
Proliferative normal liver cells of HCC patients with liver cirrhosis express low level of TERT during premalignant or late stages of HCC

In need of multifunctional TERT-targeted therapy due to the limitation of TERT inhibition
In need of HCC-specific therapies that can minimize dysfunction of normal liver cell

Advantages of Technology

Improved HCC specificity
HCC-selective expression of therapeutic RNA through specific replacement of hTERT RNA with therapeutic RNA

Multiple antitumor effects
Removal of cancer cell hTERT RNA and simultaneous expression of therapeutic RNA

hTERT targeting
Effective application to heterogenous cancer cells through targeting hTERT expressed in 80 ~ 90% of HCC

Improved anticancer efficacy
Use of HSVtk as therapeutic gene: Cancer regression, bystander effect, and cancer immunity induction

Indication expansion
Indication expansion for various carcinomas. Modular engineering → Application to various diseases