Polyethylenimine-mediated cochlear gene transfer in guinea pigs.

OBJECTIVE

To demonstrate and compare polycationic-mediated cochlear gene transfer with linear polyethylenimine (PEI) via cochleostomy and osmotic pump infusion method.

DESIGN

A dissociated cochlear culture was used to select the optimum nitrogen to phosphate ratio of PEI/DNA complexes to be used in vivo. The PEI-enhanced green fluorescent protein reporter gene DNA complex was introduced with single inoculation (cochleostomy) or with sustained delivery (osmotic pump method) into guinea pig cochleas and examined for transgene expression.

SUBJECTS

Male Albino Hartley guinea pigs (250-350 g).

RESULTS

The relatively low transfection efficiency of PEI limits its potential when compared with viral counterparts; however, sustained release of the vector solution was able to improve PEI's transfection efficiency. The PEI-infused cochleas maintained intact cellular and tissue architecture with absence of inflammation. Transfection confined to the perilymphatic space highlights the need to target the gene vector into the scala media if transfection is targeted at cells within the organ of Corti.

CONCLUSION

These findings indicate that PEI is able to transfect the cochlea in vivo with sustained delivery and present an alternative for nonviral cochlear gene therapy.