Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss.
Refining surgical techniques for efficient posterior semicircular canal gene delivery in the adult mammalian inner ear with minimal hearing loss.
复制标题
DOI：
10.1038/s41598-021-98412-y
复制
发表时间：
2021-09-22
影响因子：
4.6
通讯作者：
Chien W
中科院分区：
文献类型：
--
作者：
Zhu J;Choi JW;Ishibashi Y;Isgrig K;Grati M;Bennett J;Chien W
听力损失是当今影响世界人口的一种常见残疾。虽然有几项研究表明，内耳基因治疗可以成功地应用于遗传性听力损失的小鼠模型，以改善听力，但这些研究大多依赖于新生儿年龄的内耳基因传递，此时小鼠内耳尚未发育完全。然而，人的内耳在出生时就发育完全了。因此，为了将内耳基因治疗成功地应用于听力损失患者，必须证明在成熟的哺乳动物内耳中可以安全可靠地进行基因传递。在这项研究中，我们研究了成年小鼠内耳后半规管基因传递的步骤。我们发现淋巴管周围渗漏的持续时间和注射率对术后听力结果有显著影响。我们的研究结果表明，尽管在相同病毒载量下，AAV2.7m8在成年小鼠中的毛细胞转导率低于新生小鼠，但AAV2.7m8能够以剂量依赖性的方式高效转导成年小鼠的内外部毛细胞。
Hearing loss is a common disability affecting the world’s population today. While several studies have shown that inner ear gene therapy can be successfully applied to mouse models of hereditary hearing loss to improve hearing, most of these studies rely on inner ear gene delivery in the neonatal age, when mouse inner ear has not fully developed. However, the human inner ear is fully developed at birth. Therefore, in order for inner ear gene therapy to be successfully applied in patients with hearing loss, one must demonstrate that gene delivery can be safely and reliably performed in the mature mammalian inner ear. In this study, we examine the steps involved in posterior semicircular canal gene delivery in the adult mouse inner ear. We find that the duration of perilymphatic leakage and injection rate have a significant effect on the post-surgical hearing outcome. Our results show that although AAV2.7m8 has a lower hair cell transduction rate in adult mice compared to neonatal mice at equivalent viral load, AAV2.7m8 is capable of transducing the adult mouse inner and outer hair cells with high efficiency in a dose-dependent manner.
登录
查看更多内容
影响因子：
12.4
作者：
Isgrig, Kevin;Shteamer, Jack W.;Chien, Wade W.
通讯作者：
Chien, Wade W.
影响因子：
16.6
作者：
Isgrig, Kevin;McDougald, Devin S.;Chien, Wade W.
通讯作者：
Chien, Wade W.
影响因子：
12.4
作者：
Kawamoto, K;Oh, SH;Raphael, Y
通讯作者：
Raphael, Y
影响因子：
3.4
作者：
Quaranta, Nicola;Liuzzi, Cristina;Quaranta, Antonio
通讯作者：
Quaranta, Antonio
影响因子：
46.9
作者：
Landegger LD;Pan B;Askew C;Wassmer SJ;Gluck SD;Galvin A;Taylor R;Forge A;Stankovic KM;Holt JR;Vandenberghe LH
通讯作者：
Vandenberghe LH