用E2F诱对人类血管旁路移植进行ex-vivo基因疗法:PREVENT单中心,随机,受控试验
M J Mann1, A D Whittemore, M C Donaldson
1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Lancet (London, England)
|November 7, 1999
概括
使用E2F-诱寡氧核酸的手术内基因治疗可以安全地抑制静脉移植中的细胞循环进展. 这种新的方法在减少对患者的旁路移植失败方面表现有前途.
科学领域:
- 血管外科 血管外科
- 基因治疗 基因治疗
- 分子生物学分子生物学
背景情况:
- 由于新极度增生和动脉样硬化导致的静脉移植失败是一个重大的临床挑战.
- 针对细胞循环阻断的ex-vivo基因疗法在实验模型中显示出潜力.
- 这项研究评估了手术内基因疗法的安全性和有效性,用于人类绕道静脉移植.
研究的目的:
- 评估使用E2F-诱寡氧核酸在人类下内静脉移植中的术内基因治疗的安全性和生物疗效.
- 确定这种基因疗法抑制目标细胞周期调节基因和DNA合成的能力.
- 评估对临床结果的影响,如移植闭塞和狭窄.
主要方法:
- 一项前性,随机化,受控试验,涉及41名接受下静脉旁路移植的患者.
- 患者被分配到未经治疗的,E2F诱治疗的或混合的oligodeoxynucleotide治疗的组.
- 在手术期间通过活体压力介导的转染实现了寡核酸的输送.
主要成果:
- 使用E2F-诱寡氧核酸实现了高转染效率 (89.0%).
- 在E2F-诱组 (p<0.0001) 中观察到细胞循环标记 (PCNA,c-myc mRNA) 和DNA合成 (BrdU结合) 的显著抑制.
- 与未经治疗的组相比,E2F诱组在12个月内显示了移植封闭,修复或临界狭窄的发病率降低 (HR 0.34).
结论:
- 内手术E2F诱寡氧核酸转染是一种安全且可行的方法,用于人类绕道静脉移植.
- 这种基因疗法有效地实现了细胞周期基因表达和DNA复制的序列特异性抑制.
- 这种基因工程策略有可能改善一次性绕道静脉移植的长期通透率.
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