Use of tumor-targeting trans-splicing ribozyme for cancer treatment

Area of Science:

• Molecular Biology
• Gene Therapy
• Oncology

Background:

• Cancer gene therapy requires enhanced efficacy and safety.
• Gene targeting offers a promising strategy to selectively eliminate cancer cells.
• Developing precise targeting mechanisms is crucial for minimizing off-target effects.

Purpose of the Study:

• To develop a tumor-targeting gene therapy approach using a trans-splicing ribozyme.
• To reprogram human cytoskeleton-associate protein 2 (hCKAP2)-encoding RNA for selective cancer cell targeting.
• To evaluate the in vivo efficacy and safety of an adenoviral vector-delivered system.

Main Methods:

• Construction of a specific trans-splicing ribozyme targeting hCKAP2 RNA.
• Development of adenoviral vectors for in vivo delivery of the ribozyme.
• Assessment of cancer retardation, target RNA specificity, and in vivo toxicity in tumor xenograft and hepatocarcinoma models.

Main Results:

• Demonstrated successful targeting and reprogramming of hCKAP2 RNA in cancer cells.
• Adenoviral vectors showed selective activation of the therapeutic transgene (herpes simplex virus thymidine kinase) in target cells.
• Evaluated cancer retardation and specificity, alongside in vivo toxicity profiles.

Conclusions:

• The trans-splicing ribozyme approach shows potential for safe and effective cancer gene therapy.
• Selective targeting of hCKAP2 RNA enables precise therapeutic transgene delivery.
• Further development of this system could lead to improved cancer treatment strategies.