Canalostomy is an ideal surgery route for inner ear gene delivery in big animal model

Abstract

Background: Inner gene therapy offers great promises as a potential treatment for hearing loss.

Aims/objectives: One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss.

Material and methods: Surgery was performed only in the right ear of each Bama miniature pig, and the left ear served as a control. The gene delivery to inner ear via round window membrane (RWM) and posterior semicircular canal (PSC) approach was performed with the viral vector AAV1-CMV-GFP.

Results: The gene delivery through RWM and the PSC (canalostomy) is able to perfuse the inner ear.

Conclusions and significance: The easy anatomic identification of the PSC, as to RWM, as well as minimal manipulation of the temporal bone required, make this surgical approach an attractive option for inner ear gene delivery in big animal model.

Chinese abstract

背景：作为一种潜在的治疗听力损失的方法, 内耳基因治疗有着巨大的前景。

目的：内耳基因治疗成功的关键性决定因素之一是, 找到一种在将听力损失降至最低的同时使靶细胞类型的转导效率保持稳定的输入方法。

材料与方法：对每只巴马小型猪的右耳进行手术, 左耳作为对照。采用病毒载体AAV1-CMV-GFP, 经圆窗膜（RWM）和后半规管（PSC）将基因输入内耳。

结果：经RWM和PSC（导管切开术）的基因输入能够灌注内耳。

结论与意义：对于RWM而言, PSC的解剖识别和对颞骨的最低程度的影响, 使得这种手术方法成为大动物模型内耳基因输入的一种有吸引力的选择

Keywords:

• Gene therapy
• inner ear
• canalostomy
• Bama pig
• gene delivery
• hearing loss

Ethical approval

All animal surgeries and procedures were conducted according to the guidelines of the Ethics Committee of the PLA General Hospital and approved by the Animal Ethics Committee of the Institute of Zoology, Chinese Academy of Sciences.

Availability of data and material

All data generated or analysed during this study are included in this published article.

Authors' contributions

JXJ, CW, and GWW performed the investigation and interpreted the data. WX, ZY, and LQ performed the histological examination. Moreover, ZJG and YSM were the major contributors in writing the manuscript. All authors read and approved the final manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by grants from Key International (Regional) Joint Research Program of National Natural Science Foundation of China (NSFC#81820108009), the National Natural Science Foundation of China (NSFC #81670940) and Special Cultivating and Developing Program of Beijing Science and Technology Innovation Base (z151100001615050). These fundings play role of the funding body in the design of the study and collection, analysis, and interpretation of data.