Efficient and specific transduction of cochlear supporting cells by adeno-associated virus serotype 5

• Published in: Neuroscience letters Vol. 442; no. 2; pp. 134 - 139
• Main Authors: Ballana, Ester, Wang, Jing, Venail, Frédéric, Estivill, Xavier, Puel, Jean-Luc, Arbonès, Maria L., Bosch, Assumpció
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 12.09.2008; Elsevier
• Subjects: AAV5 serotype; Adeno-associated virus; Animals; Animals, Newborn; Biological and medical sciences; Calbindins; Calcium-Binding Protein, Vitamin D-Dependent; Cochlea; Cochlea - cytology; Cochlea - virology; Connexin 26; Connexins; Connexins - metabolism; Dependovirus; Dependovirus - classification; Dependovirus - physiology; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene transfer; Genetic Vectors; Genetic Vectors - physiology; Glial Fibrillary Acidic Protein; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Guinea Pigs; Hair Cells, Auditory, Inner; Hair Cells, Auditory, Inner - metabolism; Hair Cells, Auditory, Inner - virology; Inner ear; Intermediate Filament Proteins; Intermediate Filament Proteins - metabolism; Life Sciences; Membrane Glycoproteins; Membrane Glycoproteins - metabolism; Mice; Myelin Basic Protein - metabolism; Myelin Basic Proteins; Myosins; Myosins - metabolism; Nerve Tissue Proteins; Nerve Tissue Proteins - metabolism; Neurofilament Proteins; Neurofilament Proteins - metabolism; Neurons and Cognition; Organ Culture Techniques; Peripherins; Phalloidine; Phalloidine - metabolism; Receptor, Platelet-Derived Growth Factor alpha; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - metabolism; S100 Calcium Binding Protein G - metabolism; Supporting cells; Transduction, Genetic; Transduction, Genetic - methods; Vertebrates: nervous system and sense organs; Supporting cells; Gene transfer; Inner ear; AAV5 serotype; Gene transfer,AAV5 serotype,Inner ear,Supporting cells; Supporting cell; Organ of hearing; Genetic transfer
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.06.060

Congenital deafness, affecting 1 in 1000 neonates, can lead to major problems in speech, cognitive and psychosocial development. Congenital deafness is mainly caused by mutations in connexins, hemi-channel proteins forming gap-junctions between supporting cells in the sensory epithelia. We describe a high tropism of AAV5 serotype for the supporting cells of the cochlea, both in vitro in postnatal day 4 mouse explants, and in vivo in the adult guinea-pig inner ear, through scala media perfusion. AAV5 transduction correlates with PDGFRα expression, previously reported as AAV5 receptor. This vector could be of major interest in addressing gene therapy approaches to deafness as well as for studying basic aspects of inner-ear development and hearing mechanisms.