Systemic Human Htert Aav Gene Transfer Therapy And The Effect On Telomere Length And Biological Age, A Case Report

P. Sewell
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Abstract

A single adult female human was treated with AAV hTERT gene transfer therapy on two separate occasions 5 years apart. Follow-up is 5.8 years. The first dose administered on 9.16.2015 consisted of a total intravenous dose of 3e15 AAV hTERT. The second dose administered on 9.24.2020 consisted of a total intravenous dose of 3e15 AAV hTERT. Before and after each therapy and periodically in between the doses, Human Leucocyte telomere analysis was performed. The initial telomere length measurements collected on 9.15.2015 at the initiation of the AAV hTERT gene transfer therapy demonstrated a baseline average telomere length of 6.71kb which corresponded to a telomere percentage relative to age and population at the 30th percentile. The most recent telomere length measurements collected on 7.13.2021 demonstrated an average telomere length of 8.94kb which corresponded to a telomere percentage relative to age and population at the 89th percentile. The results demonstrate the progressive lengthening of the recipient’s telomeres from 6.71kb to 8.94kb despite advancing 5.8 years in chronological age. Associated age as related to telomere length (also known as biological age) was calculated and compared to chronological age. Initially on 9.15.2015, and prior to the first AAV hTERT gene transfer therapy, the associated age was calculated to be 62 years. The latest telomere analysis dated 7.13.2021 demonstrated a calculated associated age of 25 years. This decrease in associated, or biological age, decreased at a rate of 5.3 years per year of chronological age advancement.
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系统性人Htert Aav基因转移治疗及其对端粒长度和生物年龄的影响1例报告
一名成年女性在相隔5年的两次不同场合接受AAV hTERT基因转移治疗。随访时间为5.8年。2015年9月16日首次给药,静脉总剂量为3e15 AAV hTERT。第二剂于2020年9月24日给药,静脉总剂量为3e15 AAV hTERT。在每次治疗前后和剂量之间定期进行人白细胞端粒分析。在AAV hTERT基因转移治疗开始时,于2015年9月15日收集的初始端粒长度测量显示,基线平均端粒长度为6.71kb,对应于端粒相对于年龄和人口的第30百分位百分比。最新的端粒长度测量于2021年7月13日收集,显示平均端粒长度为8.94kb,对应于端粒相对于年龄和人口的第89百分位百分比。结果表明,尽管实际年龄增长了5.8岁,但接受者的端粒从6.71kb逐渐延长到8.94kb。计算与端粒长度相关的相关年龄(也称为生物年龄),并将其与实足年龄进行比较。最初于2015年9月15日,在第一次AAV hTERT基因转移治疗之前,计算相关年龄为62岁。最新的端粒分析日期为2021年7月13日,计算出的相关年龄为25岁。这种相关年龄或生物年龄的下降以每年实际年龄增长5.3岁的速度下降。
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