BACKGROUND: Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects. METHODS: Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of the cochlea basal turn, an approach that could be used in cochlear implant surgery. At 7 days after injection, distribution of gene expression, hearing and morphology were evaluated. Adenoviral vector was also used to compare distributions of gene expression. Moreover, distribution of cell surface receptors of AAV in the cochlea was examined using immunohistochemistry. RESULTS: Using the perilymphatic approach, adenovirus could be transferred to mesothelial cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly efficient transfer to sensory cells. This tissue tropism of AAV could not be explained by the distribution of AAV receptors. Hearing and morphology were largely unaffected. CONCLUSIONS: Our results indicate that AAV vector can be safely applied to the inner ear and AAV-2/2 offers a good tool for transferring transgenes into sensory cells of the inner ear efficiently without toxicity.
BACKGROUND: Several genes are candidates for treating inner ear diseases. For clinical applications, minimally invasive approaches to the inner ear are desirable along with minimal side-effects. METHODS:Adeno-associated virus (AAV) was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of the cochlea basal turn, an approach that could be used in cochlear implant surgery. At 7 days after injection, distribution of gene expression, hearing and morphology were evaluated. Adenoviral vector was also used to compare distributions of gene expression. Moreover, distribution of cell surface receptors of AAV in the cochlea was examined using immunohistochemistry. RESULTS: Using the perilymphatic approach, adenovirus could be transferred to mesothelial cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly efficient transfer to sensory cells. This tissue tropism of AAV could not be explained by the distribution of AAV receptors. Hearing and morphology were largely unaffected. CONCLUSIONS: Our results indicate that AAV vector can be safely applied to the inner ear and AAV-2/2 offers a good tool for transferring transgenes into sensory cells of the inner ear efficiently without toxicity.
Authors: Seiji B Shibata; Sarah R Cortez; James A Wiler; Donald L Swiderski; Yehoash Raphael Journal: Hum Gene Ther Date: 2012-02-08 Impact factor: 5.695
Authors: Alice Emptoz; Vincent Michel; Andrea Lelli; Omar Akil; Jacques Boutet de Monvel; Ghizlene Lahlou; Anaïs Meyer; Typhaine Dupont; Sylvie Nouaille; Elody Ey; Filipa Franca de Barros; Mathieu Beraneck; Didier Dulon; Jean-Pierre Hardelin; Lawrence Lustig; Paul Avan; Christine Petit; Saaid Safieddine Journal: Proc Natl Acad Sci U S A Date: 2017-08-23 Impact factor: 11.205
Authors: Omar Akil; Rebecca P Seal; Kevin Burke; Chuansong Wang; Aurash Alemi; Matthew During; Robert H Edwards; Lawrence R Lustig Journal: Neuron Date: 2012-07-26 Impact factor: 17.173