Research press release


Nature Biotechnology

Gene therapy restores hearing and balance in mice



1つめの報告ではKonstantina Stankovic、Jeffrey Holt、Luk Vandenbergheたちが、アデノ随伴ウイルス(小型のウイルスで、ヒトに感染するが病気は起こさない)の合成変異体を用いて、マウスの外有毛細胞、内有毛細胞に蛍光タンパク質の遺伝子を効率良く導入できることを明らかにした。安全性を調べたところ、正円窓膜からの注入を含め、この治療法による有害作用はないことが分かった。

2つめの報告では、Gwenaelle Geleocたちが同じアデノ随伴ウイルスベクターを使って、アッシャー症候群タイプICの原因となる変異遺伝子を持つマウスを治療した。アッシャー症候群タイプICは小児の遺伝性疾患で、難聴、平衡障害、失明を引き起こす。変異した遺伝子Ush1cの正常コピーを、出生直後のマウスの蝸牛に導入すると、外有毛細胞と内有毛細胞のUsh1cタンパク質のレベルが上昇し、損傷した感覚毛が修復されて、極度の難聴だったマウスの聴覚と平衡感覚がしっかりと改善され、ささやき程度の音が聞こえるようになったという。

Efficient delivery of genes to the mouse inner ear and unprecedented correction of hearing loss and balance symptoms in a mouse model of a rare genetic hearing disorder are reported in two papers published online this week in Nature Biotechnology. If the viral delivery technology used in these studies can be translated to the clinic, it would represent a breakthrough in gene-transfer approaches to treat genetic diseases of the inner ear.

Genetic hearing disorders are estimated to affect 125 million people worldwide and have been linked to mutations in more than 100 genes. A large body of research has shown that various genetic diseases can be cured in animals and humans using benign viruses engineered to carry normal copies of genes into different organs. Until now, however, scientists have not succeeded in identifying a virus capable of efficiently entering the cells of the inner ear (cochlea), particularly a subset of cells known as ‘outer hair cells’, which tune the responses of ‘inner hair cells’ to sound waves. In many cases of genetic hearing loss, delivery of genes to both outer and inner hair cells is needed to confer normal hearing ability.

In the first paper, Konstantina Stankovic, Jeffrey Holt, Luk Vandenberghe, and colleagues show that a synthetic variant of adeno-associated virus - a small virus that infects humans without causing disease - efficiently delivers a gene encoding a fluorescent protein to mouse outer and inner hair cells. Safety studies found that the procedure, including injection through the round window membrane, had no adverse effects.

In the second paper, Gwenaelle Geleoc and colleagues use the same viral vector to treat mice carrying a mutated gene responsible for Usher syndrome type IC, a childhood genetic disease that causes deafness, balance dysfunction, and blindness. Delivery of a normal copy of the mutated gene, Ush1c, to the cochlea soon after the mice were born led to high levels of Ush1c protein in outer and inner hair cells, repair of damaged hair cell bundles, and a robust improvement in hearing and balance behaviour, enabling profoundly deaf mice to hear sounds at the level of whispers.

doi: 10.1038/nbt.3781


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