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

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.

KEYWORDS:

• Gene therapy
• adeno-associated viral vector
• control release
• nanoparticles
• tendon repair
• adhesions

Declaration of interest

This work was supported by grants from the Natural Science Foundation of China [No. 81271985, 81030035, 81401797 and 81401796], and Jiangsu Medical Research Center Grant from Jiangsu Province, China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• Gene therapy using growth factor genes and a non-pathogenic vector increased tendon healing strength in the critical period of early tendon healing after surgical repair in animal models.

• Micro-RNA related gene therapy through the vector or nanoparticles decreased adhesions around the healing tendon, but the tendon strength was decreased in the animal models that we have tested thus far.

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