Cargando…

New intranasal and injectable gene therapy for healthy life extension

As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can...

Descripción completa

Detalles Bibliográficos
Autores principales: Jaijyan, Dabbu Kumar, Selariu, Anca, Cruz-Cosme, Ruth, Tong, Mingming, Yang, Shaomin, Stefa, Alketa, Kekich, David, Sadoshima, Junichi, Herbig, Utz, Tang, Qiyi, Church, George, Parrish, Elizabeth L., Zhu, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171804/
https://www.ncbi.nlm.nih.gov/pubmed/35537048
http://dx.doi.org/10.1073/pnas.2121499119
_version_ 1784721748134985728
author Jaijyan, Dabbu Kumar
Selariu, Anca
Cruz-Cosme, Ruth
Tong, Mingming
Yang, Shaomin
Stefa, Alketa
Kekich, David
Sadoshima, Junichi
Herbig, Utz
Tang, Qiyi
Church, George
Parrish, Elizabeth L.
Zhu, Hua
author_facet Jaijyan, Dabbu Kumar
Selariu, Anca
Cruz-Cosme, Ruth
Tong, Mingming
Yang, Shaomin
Stefa, Alketa
Kekich, David
Sadoshima, Junichi
Herbig, Utz
Tang, Qiyi
Church, George
Parrish, Elizabeth L.
Zhu, Hua
author_sort Jaijyan, Dabbu Kumar
collection PubMed
description As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. In our study, we sought to determine whether the high-capacity cytomegalovirus vector (CMV) can be an effective and safe gene delivery method for two such protective factors: telomerase reverse transcriptase (TERT) and follistatin (FST). We found that the mouse cytomegalovirus (MCMV) carrying exogenous TERT or FST (MCMV(TERT) or MCMV(FST)) extended median lifespan by 41.4% and 32.5%, respectively. We report CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Specifically, this treatment significantly improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia. Further, telomere shortening associated with aging was ameliorated by TERT and mitochondrial structure deterioration was halted in both treatments. Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span.
format Online
Article
Text
id pubmed-9171804
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-91718042022-06-08 New intranasal and injectable gene therapy for healthy life extension Jaijyan, Dabbu Kumar Selariu, Anca Cruz-Cosme, Ruth Tong, Mingming Yang, Shaomin Stefa, Alketa Kekich, David Sadoshima, Junichi Herbig, Utz Tang, Qiyi Church, George Parrish, Elizabeth L. Zhu, Hua Proc Natl Acad Sci U S A Biological Sciences As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. In our study, we sought to determine whether the high-capacity cytomegalovirus vector (CMV) can be an effective and safe gene delivery method for two such protective factors: telomerase reverse transcriptase (TERT) and follistatin (FST). We found that the mouse cytomegalovirus (MCMV) carrying exogenous TERT or FST (MCMV(TERT) or MCMV(FST)) extended median lifespan by 41.4% and 32.5%, respectively. We report CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Specifically, this treatment significantly improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia. Further, telomere shortening associated with aging was ameliorated by TERT and mitochondrial structure deterioration was halted in both treatments. Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span. National Academy of Sciences 2022-05-10 2022-05-17 /pmc/articles/PMC9171804/ /pubmed/35537048 http://dx.doi.org/10.1073/pnas.2121499119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Jaijyan, Dabbu Kumar
Selariu, Anca
Cruz-Cosme, Ruth
Tong, Mingming
Yang, Shaomin
Stefa, Alketa
Kekich, David
Sadoshima, Junichi
Herbig, Utz
Tang, Qiyi
Church, George
Parrish, Elizabeth L.
Zhu, Hua
New intranasal and injectable gene therapy for healthy life extension
title New intranasal and injectable gene therapy for healthy life extension
title_full New intranasal and injectable gene therapy for healthy life extension
title_fullStr New intranasal and injectable gene therapy for healthy life extension
title_full_unstemmed New intranasal and injectable gene therapy for healthy life extension
title_short New intranasal and injectable gene therapy for healthy life extension
title_sort new intranasal and injectable gene therapy for healthy life extension
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171804/
https://www.ncbi.nlm.nih.gov/pubmed/35537048
http://dx.doi.org/10.1073/pnas.2121499119
work_keys_str_mv AT jaijyandabbukumar newintranasalandinjectablegenetherapyforhealthylifeextension
AT selariuanca newintranasalandinjectablegenetherapyforhealthylifeextension
AT cruzcosmeruth newintranasalandinjectablegenetherapyforhealthylifeextension
AT tongmingming newintranasalandinjectablegenetherapyforhealthylifeextension
AT yangshaomin newintranasalandinjectablegenetherapyforhealthylifeextension
AT stefaalketa newintranasalandinjectablegenetherapyforhealthylifeextension
AT kekichdavid newintranasalandinjectablegenetherapyforhealthylifeextension
AT sadoshimajunichi newintranasalandinjectablegenetherapyforhealthylifeextension
AT herbigutz newintranasalandinjectablegenetherapyforhealthylifeextension
AT tangqiyi newintranasalandinjectablegenetherapyforhealthylifeextension
AT churchgeorge newintranasalandinjectablegenetherapyforhealthylifeextension
AT parrishelizabethl newintranasalandinjectablegenetherapyforhealthylifeextension
AT zhuhua newintranasalandinjectablegenetherapyforhealthylifeextension