Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?
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DOI：
10.3389/fimmu.2022.931524
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肺移植是终末期肺病患者的最终治疗方法。尽管该领域取得了重大进展，但移植物存活率仍然是所有实体器官移植中最低的。此外，肺的器官利用率最低——在合格的捐赠者中，2019 年只有 22% 的多器官捐赠者的肺被移植。需要新的策略来修复边缘器官并提高移植物的存活率。基因治疗是优化供体同种异体移植物的一种有前景的策略。可以实现特定基因的过度表达或抑制，以针对移植物损伤的各种途径，包括缺血再灌注损伤、体液或细胞排斥以及慢性肺同种异体移植物功能障碍。动物模型实验历来使用基于腺病毒的载体，并且大多数肺移植文献都集中于 IL-10 的过度表达。尽管在临床前模型中显示出多种策略可以预防排斥反应并延长移植物存活率，但没有一种策略能够转化为临床。过去十年见证了基因治疗领域的复兴，两种基于 AAV 的体内基因疗法现已获得 FDA 批准用于临床。与此同时，常温离体机器灌注技术已成为传统静态冷藏的替代方案。这种保存方法使器官在储存过程中保持生理活性，从而可能为基因治疗提供一个平台。本综述将探讨各种基因治疗方式的优点和缺点，回顾与同种异体移植损伤各个阶段有关的各种候选基因，并总结最近使用基因治疗优化供肺的努力。
Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates—among eligible donors, only 22% of lungs from multi-organ donors were transplanted in 2019. Novel strategies are needed to rehabilitate marginal organs and improve graft survival. Gene therapy is one promising strategy in optimizing donor allografts. Over-expression or inhibition of specific genes can be achieved to target various pathways of graft injury, including ischemic-reperfusion injuries, humoral or cellular rejection, and chronic lung allograft dysfunction. Experiments in animal models have historically utilized adenovirus-based vectors and the majority of literature in lung transplantation has focused on overexpression of IL-10. Although several strategies were shown to prevent rejection and prolong graft survival in preclinical models, none have led to clinical translation. The past decade has seen a renaissance in the field of gene therapy and two AAV-based in vivo gene therapies are now FDA-approved for clinical use. Concurrently, normothermic ex vivo machine perfusion technology has emerged as an alternative to traditional static cold storage. This preservation method keeps organs physiologically active during storage and thus potentially offers a platform for gene therapy. This review will explore the advantages and disadvantages of various gene therapy modalities, review various candidate genes implicated in various stages of allograft injury and summarize the recent efforts in optimizing donor lungs using gene therapy.
DOI：
10.3390/v2020395
发表时间：
2010-02
期刊：
Viruses
影响因子：
--
作者：
Castellani S;Conese M
通讯作者：
Conese M
“病毒载体的支气管动脉在囊性纤维化中输送基因递送；优于气道输送？”。
影响因子：
3.1
作者：
Bakhai A;Sheridan DJ;Coutelle CC
通讯作者：
Coutelle CC