AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung...

Area of Science:

• Molecular Biology
• Genetics
• Gerontology

Background:

• Short telomeres trigger DNA damage response, leading to senescence, apoptosis, and age-related diseases.
• Telomere syndromes arise from germline mutations causing extremely short telomeres.
• Telomerase activation is a potential therapeutic strategy for telomere syndromes and aging.

Purpose of the Study:

• To evaluate the safety of adeno-associated virus 9 (AAV9)-mediated telomerase (Tert) gene therapy in a cancer-prone mouse model.
• To determine if Tert overexpression accelerates cancer onset or progression in oncogene-induced tumors.

Main Methods:

• Adeno-associated viral vectors carrying the telomerase gene (AAV9-Tert) were administered to mice.
• A cancer-prone mouse model with oncogenic K-ras and a p53-null background was used.
• Control groups received AAV9 vectors with a catalytically inactive form of Tert.

Main Results:

• Overexpression of Tert did not accelerate the onset or progression of lung carcinomas.
• No increased cancer incidence was observed, even in a p53-null background.
• AAV9-mediated Tert gene therapy demonstrated no detectable cancer-prone effects.

Conclusions:

• Telomerase activation via AAV9-mediated Tert gene therapy is safe in the context of oncogene-induced tumors.
• This therapeutic strategy holds promise for treating telomere syndromes and age-related diseases without increasing cancer risk.