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

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....

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Autores principales: Hong, JinWoo, Yun, Chae-Ok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563133/
https://www.ncbi.nlm.nih.gov/pubmed/31035374
http://dx.doi.org/10.3390/cells8050392
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author Hong, JinWoo
Yun, Chae-Ok
author_facet Hong, JinWoo
Yun, Chae-Ok
author_sort Hong, JinWoo
collection PubMed
description 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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spelling pubmed-65631332019-06-17 Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases Hong, JinWoo Yun, Chae-Ok Cells Review 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. MDPI 2019-04-28 /pmc/articles/PMC6563133/ /pubmed/31035374 http://dx.doi.org/10.3390/cells8050392 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hong, JinWoo
Yun, Chae-Ok
Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title_full Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title_fullStr Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title_full_unstemmed Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title_short Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
title_sort telomere gene therapy: polarizing therapeutic goals for treatment of various diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563133/
https://www.ncbi.nlm.nih.gov/pubmed/31035374
http://dx.doi.org/10.3390/cells8050392
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