期刊
CELLS
卷 8, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cells8050392
关键词
telomere; telomerase; telomere dysfunction; gene therapy; anti-aging; regenerative medicine; cancer therapy
类别
资金
- National Research Foundation of Korea [2016M3A9B5942352]
- Hanyang University of Korea [HY-2011-G-201100000001880]
Modulation of telomerase maintenance by gene therapy must meet two polarizing requirements to achieve different therapeutic outcomes: Anti-aging/regenerative applications require upregulation, while anticancer applications necessitate suppression of various genes integral to telomere maintenance (e.g., telomerase, telomerase RNA components, and shelterin complex). Patients suffering from aging-associated illnesses often exhibit telomere attrition, which promotes chromosomal instability and cellular senescence, thus requiring the transfer of telomere maintenance-related genes to improve patient outcomes. However, reactivation and overexpression of telomerase are observed in 85% of cancer patients; this process is integral to cancer immortality. Thus, telomere-associated genes in the scope of cancer gene therapy must be inactivated or inhibited to induce anticancer effects. These contradicting requirements for achieving different therapeutic outcomes mean that any vector-mediated upregulation of telomere-associated genes must be accompanied by rigorous evaluation of potential oncogenesis. Thus, this review aims to discuss how telomere-associated genes are being targeted or utilized in various gene therapy applications and provides some insight into currently available safety hazard assessments.
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