New intranasal and injectable gene therapy for healthy life extension.
New intranasal and injectable gene therapy for healthy life extension.
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DOI：
10.1073/pnas.2121499119
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发表时间：
2022-05-17
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
使用CMV作为基因治疗载体，我们说明了CMV可以在治疗上用作每月吸入或腹腔内递送的治疗，用于衰老相关的衰退。外源性端粒酶逆转录酶或卵泡抑素基因在小鼠模型中安全有效地传递。这种治疗显着改善了与健康衰老相关的生物标志物，小鼠寿命增加了41%，而癌症风险没有增加。这项研究对老龄化人口的影响不容低估，因为全球与老龄化相关的非传染性疾病负担迅速上升。随着全球老年人口的增长，提供多样化和有效的手段来减轻老龄化对人类健康的影响在社会经济和医学上都至关重要。先前的研究表明，腺相关病毒（AAV）载体诱导某些蛋白质的过表达，这可以抑制或逆转动物模型中的衰老效应。在我们的研究中，我们试图确定高容量的巨细胞病毒载体（CMV）是否可以成为一种有效和安全的基因传递方法，两个这样的保护因素：端粒酶逆转录酶（TERT）和卵泡抑素（FST）。我们发现，携带外源性TERT或FST的小鼠巨细胞病毒（MCMV）（MCMVTERT或MCMVFST）分别延长了41.4%和32.5%的中位寿命。我们报告CMV被成功地用作鼻内和注射基因治疗系统，以延长寿命。具体而言，这种治疗显著改善了葡萄糖耐量、身体表现以及预防体重减轻和脱发。此外，与衰老相关的端粒缩短通过TERT得到改善，并且在两种治疗中线粒体结构恶化停止。鼻内和注射制剂在安全有效地向多个器官提供基因治疗方面表现同样出色，具有持久的益处，并且没有致癌性或不必要的副作用。将这项研究转化为人类可能会对生活质量和健康寿命的增加产生重大影响。
Using CMV as a gene therapy vector we illustrated that CMV can be used therapeutically as a monthly inhaled or intraperitoneally delivered treatment for aging-associated decline. Exogenous telomerase reverse transcriptase or follistatin genes were safely and effectively delivered in a murine model. This treatment significantly improved biomarkers associated with healthy aging, and the mouse lifespan was increased up to 41% without an increased risk of cancer. The impact of this research on an aging population cannot be understated as the global aging-related noncommunicable disease burden quickly rises. 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 (MCMVTERT or MCMVFST) 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.
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影响因子：
4.6
作者：
Gangopadhyay, Samudra S.
通讯作者：
Gangopadhyay, Samudra S.
影响因子：
5.2
作者：
Cruz-Muñoz ME;Fuentes-Pananá EM
通讯作者：
Fuentes-Pananá EM
影响因子：
6.4
作者：
Farrell，Helen E.;Lawler，Clara;Stevenson，Philip G.
通讯作者：
Stevenson，Philip G.
影响因子：
3.7
作者：
Hansen, Scott G.;Womack, Jennie;Fruh, Klaus
通讯作者：
Fruh, Klaus
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph