Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
Institute of Nano Science and Technology (INST), Hanyang University, Seoul 04763, Korea.
Cells. 2019 Apr 28;8(5):392. doi: 10.3390/cells8050392.
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.
基因治疗对端粒酶维持的调控必须满足两个极端的要求，才能实现不同的治疗效果：抗衰老/再生应用需要上调，而抗癌应用则需要抑制各种与端粒维持相关的基因（例如端粒酶、端粒酶 RNA 成分和庇护复合物）。患有与衰老相关疾病的患者通常表现出端粒损耗，这会导致染色体不稳定和细胞衰老，因此需要转移端粒维持相关基因以改善患者的治疗效果。然而，85%的癌症患者中观察到端粒酶的重新激活和过度表达；这一过程是癌症永生的关键。因此，癌症基因治疗范围内的端粒相关基因必须失活或抑制，以诱导抗癌作用。这些相互矛盾的治疗效果要求意味着任何载体介导的端粒相关基因上调都必须伴随着对潜在致癌性的严格评估。因此，本综述旨在讨论如何在各种基因治疗应用中靶向或利用端粒相关基因，并提供一些关于当前可用安全风险评估的见解。
