In vivo manipulation of inner ear gene expression in mice

Genetic research
C. Luchschen


An international team of researchers from several institutes and universities, led by a group at the Venetian Institute of Molecular Medicine, Foundation for Advanced Biomedical Research in Padua, Italy, recently published findings of their study to control gene expression in mice in vivo using viral vectors.

In a previous study, the group showed that in vitro transduction with bovine adeno-associated viral (BAAV) vectors restores connexin expression in cochlear organotypic cultures from connexin-deficient mice, models of DFNB1 non-syndromic hearing loss and deafness. In the new study, the authors aimed to manipulate inner ear connexin expression in vivo using BAAV vectors, and to identify the optimal route of vector delivery.

In humans, novel gene therapy approaches for many disorders including cancer, cardiovascular disorders, monogenic disorders, neurological disorders, and eye diseases use virus-mediated gene delivery, and associated clinical trials are underway. To date, gene delivery to the mammalian inner ear has been performed with a variety of viral vectors, and the authors believe that an important component of future therapeutic interventions will be the optimal route of vector delivery to the inner ear, which has not yet been identified.

The authors conclude that their results indicate that delivery of substances to the inner ear via canalostomy causes no adverse effects on hearing and could function as an effective route of vector delivery. In addition, in vivo transduction with BAAV vectors via canalostomy achieved widespread expression of a reporter gene.

Source: Crispino G, et al. In vivo genetic manipulation of inner ear connexin expression by bovine adeno-associated viral vectors. Scientific Reports 7, Article number: 6567 (2017).