Cochlear Gene Delivery through an Intact Round Window Membrane in Mouse

Abstract

Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes

“…Platelet cell count (256.47 79.8 and 221.17102.2/ml on day 0 for CHAS and CHAE respectively) decreased on day 1 (210.9725.4 and 161.1733.2 for CHAS and CHAE, respectively), but normalized on day 3 and 7, which is a similar pattern to that found in monkeys. 12 However, the other results (Materials and methods) were not significantly altered. Serum biochemistry testing after adenoviral delivery by CHAE also showed relatively few effects except for a slight effect on liver function.…”

“…7,8 Although it is not via blood vessel, an efficient and localized transgene expression has been successfully achieved using gelatin sponge sheets (GSS) in a rat Achilles tendon (for 17 days) and mouse cochlea. 11,12 Taken these findings together, we hypothesized that catheter-mediated hepatic arterial embolization with GSP would enhance transgene expression efficiency into hepatocytes, because of the low clearance rate and long contact time of adenovirus soaked in GSP.…”

Thérapie génique des surdités humaines

“…À ce jour, plusieurs types de vecteurs ont été utilisés comme moyen de transfert d'agents thérapeutiques dans la cochlée. Les vecteurs non viraux, tels que des plasmides seuls ou enrobés dans des composés lipidiques, ont l'avantage de présenter une toxicité faible et d'entraî-ner une inflammation réduite par rapport aux vecteurs viraux [7][8][9]. Malheureusement, ces vecteurs ont montré une efficacité de transfert limitée et un faible taux d'expression du transgène, ce qui limite leur utilité [10,11].…”

The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

“…1 Viral vectors have been used to deliver genes due to their high transfection ability. 2 However, non-viral vectors have been considered as potential carriers due to problems with viral vectors, such as carcinogenesis, immunogenicity, broad tropism, limited DNA packaging capacity, and production difficulty. 1 A nonviral delivery system, a polymer nanoparticle carrier, has been investigated due to its biocompatibility and high stability.…”