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Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases

1 and 1,2,*
1
Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
2
Institute of Nano Science and Technology (INST), Hanyang University, Seoul 04763, Korea
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 392; https://doi.org/10.3390/cells8050392
Received: 29 March 2019 / Revised: 22 April 2019 / Accepted: 24 April 2019 / Published: 28 April 2019
(This article belongs to the Special Issue The Role of Telomere Biology in Aging and Human Disease)
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PDF [270 KB, uploaded 28 April 2019]

Abstract

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. View Full-Text
Keywords: telomere; telomerase; telomere dysfunction; gene therapy; anti-aging; regenerative medicine; cancer therapy telomere; telomerase; telomere dysfunction; gene therapy; anti-aging; regenerative medicine; cancer therapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hong, J.; Yun, C.-O. Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases. Cells 2019, 8, 392.

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