下肢缺血性疾病基因治疗性血管生成的现状、挑战和展望

Current situation,challenges and prospects of gene-based therapeutic angiogenesis in lower extremity peripheral artery disease

外周动脉疾病(PAD)发病率高,开放手术和腔内治疗的血运重建是首选方案,但部分患者的治疗存在困难。治疗性血管生成(TA)旨在通过血管新生来恢复缺血组织的灌注,在PAD的治疗中引起了极大的关注。基于TA理念的方法主要有基因治疗、细胞治疗。基因治疗作用明确,易于同质化,安全性高,在药品开发中受到更多关注。在临床前的研究中,基因疗法在PAD中显示出极大的转化潜力,但到目前为止,基因治疗仅仅取得了非常有限的成功。本文对基于促血管生长因子的基因疗法在PAD治疗中的临床研究进行了梳理,试图就基础研究进展和临床现状来探讨基因疗法从实验室成功走向临床成功的潜在挑战,并对未来基因疗法如何更好地实现TA目标作出展望。

The incidence of lower extremity peripheral artery disease(LEPAD)has been rising,and to cure this,revascularization based on open surgery and endovascular treatment is the first-choice strategy,while it can be difficult to implement in some patients.Therapeutic angiogenesis(TA)aims to restore perfusion to ischemic tissues via neovascularization,and this concept has attracted huge concentration in the field of PAD treatment since its proposal.Approaches based on the TA concept primarily include gene therapy and cell therapy,and gene therapy has been favored more in drug development for its predicted effect,ease of homogenization,and high level of safety.In addition,it indicates huge translational potential in preclinical research,yet only limited success has been rendered in clinical trials.This article aims to review available clinical trials of gene therapies based on pro-angiogenic factors,discuss challenges in the process of gene therapies from the laboratory success to clinical success based on advances in basic research and clinical status,and provide prospects for how gene therapy can better achieve TA goals in the future.