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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....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6563133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hongjinwoo telomeregenetherapypolarizingtherapeuticgoalsfortreatmentofvariousdiseases AT yunchaeok telomeregenetherapypolarizingtherapeuticgoalsfortreatmentofvariousdiseases |