Title |
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear
|
---|---|
Published in |
Nature Biotechnology, February 2017
|
DOI | 10.1038/nbt.3781 |
Pubmed ID | |
Authors |
Lukas D Landegger, Bifeng Pan, Charles Askew, Sarah J Wassmer, Sarah D Gluck, Alice Galvin, Ruth Taylor, Andrew Forge, Konstantina M Stankovic, Jeffrey R Holt, Luk H Vandenberghe |
Abstract |
Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector, 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 26 | 27% |
United Kingdom | 10 | 11% |
Saudi Arabia | 7 | 7% |
Spain | 3 | 3% |
Canada | 3 | 3% |
Netherlands | 2 | 2% |
France | 2 | 2% |
North Macedonia | 1 | 1% |
Venezuela, Bolivarian Republic of | 1 | 1% |
Other | 4 | 4% |
Unknown | 36 | 38% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 70 | 74% |
Scientists | 15 | 16% |
Science communicators (journalists, bloggers, editors) | 6 | 6% |
Practitioners (doctors, other healthcare professionals) | 4 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 321 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 70 | 22% |
Researcher | 63 | 20% |
Student > Bachelor | 22 | 7% |
Student > Master | 22 | 7% |
Other | 19 | 6% |
Other | 64 | 20% |
Unknown | 61 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 67 | 21% |
Agricultural and Biological Sciences | 60 | 19% |
Medicine and Dentistry | 37 | 12% |
Neuroscience | 37 | 12% |
Unspecified | 16 | 5% |
Other | 39 | 12% |
Unknown | 65 | 20% |