RT Journal Article
SR Electronic
T1 New intranasal and injectable gene therapy for healthy life extension
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.26.449305
DO 10.1101/2021.06.26.449305
A1 Dabbu Kumar Jaijyan
A1 Anca Selariu
A1 Ruth Cruz-Cosme
A1 Mingming Tong
A1 Shaomin Yang
A1 George Church
A1 David Kekich
A1 Ali Fallah
A1 Junichi Sadoshima
A1 Qiyi Tang
A1 Elizabeth Parrish
A1 Hua Zhu
YR 2021
UL http://biorxiv.org/content/early/2021/06/26/2021.06.26.449305.abstract
AB As the global elderly population grows, it is socioeconomically and medically critical to have diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that adenovirus-associated virus (AAV) vector induced overexpression of certain proteins can suppress or reverse the effects of aging in animal models. Here, we sought to determine whether the high-capacity cytomegalovirus vector 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 (MCMVTERT or MCMVFST) extended median lifespan by 41.4% and 32.5%, respectively. This is the first report of CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Treatment significantly improved glucose tolerance, physical performance, and prevented loss of body mass and alopecia. Telomere shortening seen 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 increased health span.Competing Interest StatementThe authors have declared no competing interest.CMVcytomegalovirusDPIdays post-Inoculation and days post-InfectionFSTfollistatinIVISIn Vivo Imaging SystemMCMVmouse cytomegalovirusNCDNoncommunicable diseasesPFUplaque-forming-unitTERTtelomerase reverse transcriptaseWHOWorld Health Organization