Landegger, LD;
Pan, B;
Askew, C;
Wassmer, SJ;
Gluck, SD;
Galvin, A;
Taylor, R;
... Vandenberghe, LH; + view all
(2017)
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear.
Nature Biotechnology
, 35
(3)
pp. 280-284.
10.1038/nbt.3781.
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Abstract
Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities1,2. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector3, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. Round window membrane injection resulted in highly efficient transduction of inner and outer hair cells in mice, a substantial improvement over conventional AAV vectors. Anc80L65 round window injection was well tolerated, as indicated by sensory cell function, hearing and vestibular function, and immunologic parameters. The ability of Anc80L65 to target outer hair cells at high rates, a requirement for restoration of complex auditory function, may enable future gene therapies for hearing and balance disorders.
| Type: | Article |
|---|---|
| Title: | A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/nbt.3781 |
| Publisher version: | https://doi.org/10.1038/nbt.3781 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, HAIR CELL REGENERATION, SUPPORTING CELLS, HEARING-LOSS, THERAPY, MICE, DEAFNESS, MODEL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10065422 |
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