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Efficient and specific transduction of cochlear supporting cells by adeno-associated virus serotype 5
Ester Ballana1, Jing Wang, Frédéric Venail
1Genes and Disease Programme, Center for Genomic Regulation (CRG), UPF, Barcelona, Catalonia, Spain.
Insights
Adeno-associated virus serotype 5 (AAV5) shows high tropism for cochlear supporting cells, offering potential for gene therapy in congenital deafness. This vector targets cells expressing PDGFRalpha, a known AAV5 receptor.
Area of Science:
- Otolaryngology
- Genetics
- Molecular Biology
Background:
- Congenital deafness affects 1 in 1000 neonates, impacting speech and development.
- Connexin mutations in gap-junction proteins are a primary cause of congenital deafness.
- Gene therapy offers a promising avenue for treating deafness.
Purpose of the Study:
- To investigate the tropism of adeno-associated virus serotype 5 (AAV5) for cochlear supporting cells.
- To evaluate AAV5 as a potential vector for gene therapy targeting congenital deafness.
- To explore the role of PDGFRalpha as a receptor for AAV5 in the inner ear.
Main Methods:
- In vitro studies using postnatal day 4 mouse cochlear explants.
- In vivo studies involving scala media perfusion in adult guinea-pig inner ear.
- Correlation analysis between AAV5 transduction and PDGFRalpha expression.
Main Results:
- AAV5 demonstrated high tropism for cochlear supporting cells in both in vitro and in vivo models.
- AAV5 transduction was found to correlate with PDGFRalpha expression.
- PDGFRalpha was confirmed as a receptor for AAV5 in the inner ear.
Conclusions:
- AAV5 exhibits significant potential as a gene therapy vector for congenital deafness.
- The findings support the use of AAV5 for studying inner ear development and hearing mechanisms.
- Targeting PDGFRalpha-expressing cells offers a specific approach for inner ear gene delivery.
Abstract:
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.
