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改善屈肌腱愈合强度和质量的基因治疗策略。

Gene therapy strategies to improve strength and quality of flexor tendon healing.

作者信息

Tang Jin Bo, Zhou You Lang, Wu Ya Fang, Liu Paul Y, Wang Xiao Tian

机构信息

a Department of Hand Surgery , The Hand Surgery Research Center, Affiliated Hospital of Nantong University , Nantong , Jiangsu , China.

b Department of Plastic Surgery, Rhode Island Hospital , The Alpert Medical School of Brown University , Providence , RI , USA.

出版信息

Expert Opin Biol Ther. 2016;16(3):291-301. doi: 10.1517/14712598.2016.1134479. Epub 2016 Feb 6.

Abstract

INTRODUCTION

Rupture of the repair and adhesion around a tendon are two major problems after tendon surgery. Novel biological therapies which enhance healing and reduce adhesions are goals of many investigations. Gene therapy offers a new and promising approach to tackle these difficult problems. In the past decade, we sought to develop methods to augment tendon healing and reduce tendon adhesion through gene therapy.

AREAS COVERED

This review discusses the methods and results of adeno-associated viral (AAV) type 2 vector gene therapy to increase tendon healing strength and reduce adhesions in a chicken model. Micro-RNA related gene therapy is also discussed. We also developed a controlled release system, which incorporates nanoparticles to deliver micro-RNAs to regulate tendon healing.

EXPERT OPINION

We obtained promising results of enhancement of tendon healing strength in a chicken model using AAV2-mediated gene transfer. AAV2-mediated micro-RNA transfer also limited adhesions around the tendon. Controlled release systems incorporating nanoparticles have ideally delivered genes to the healing tendons and resulted in a moderate (but incomplete) reduction of adhesions. It remains to be determined what the best doses are and what other factors are in play in adhesion formation. These are two targets in our future investigations.

摘要

引言

肌腱修复处破裂以及肌腱周围粘连是肌腱手术后的两个主要问题。增强愈合并减少粘连的新型生物疗法是许多研究的目标。基因疗法为解决这些难题提供了一种崭新且有前景的方法。在过去十年中,我们致力于通过基因疗法开发增强肌腱愈合及减少肌腱粘连的方法。

涵盖领域

本综述讨论了腺相关病毒2型载体基因疗法在鸡模型中增强肌腱愈合强度及减少粘连的方法和结果。还讨论了与微小RNA相关的基因疗法。我们还开发了一种控释系统,该系统包含纳米颗粒以递送微小RNA来调节肌腱愈合。

专家观点

我们在鸡模型中使用AAV2介导的基因转移获得了增强肌腱愈合强度的有前景的结果。AAV2介导的微小RNA转移也限制了肌腱周围的粘连。包含纳米颗粒的控释系统已理想地将基因递送至愈合的肌腱,并使粘连有适度(但不完全)减少。最佳剂量是多少以及粘连形成中还有哪些其他因素起作用仍有待确定。这些是我们未来研究的两个目标。

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