Efficient and specific transduction of cochlear supporting cells by adeno-associated virus serotype 5.
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 PDGFRalpha 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.
Ballana
Ester
E
Genes and Disease Programme, Center for Genomic Regulation (CRG), UPF, Barcelona, Catalonia, Spain.
Wang
Jing
J
Venail
Frédéric
F
Estivill
Xavier
X
Puel
Jean-Luc
JL
Arbonès
Maria L
ML
Bosch
Assumpció
A
D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins; D003051:Cochlea / Q000166:cytology* / Q000821:virology; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism; D000229:Dependovirus / Q000145:classification / Q000502:physiology*; D015870:Gene Expression; D005822:Genetic Vectors / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism* / Q000821:virology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D064531:Peripherins; D010590:Phalloidine / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*
D064026:Calbindins; D017630:Connexins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064531:Peripherins; D064030:S100 Calcium Binding Protein G; C051774:neurofilament protein H; D000072259:Connexin 26; D049452:Green Fluorescent Proteins; D010590:Phalloidine; D020796:Receptor, Platelet-Derived Growth Factor alpha; D009218:Myosins