Polyethylenimine-mediated cochlear gene transfer in guinea pigs

Archives of Otolaryngology--head & Neck Surgery
Brian Tiong Gee TanRunsheng Ruan

Abstract

To demonstrate and compare polycationic-mediated cochlear gene transfer with linear polyethylenimine (PEI) via cochleostomy and osmotic pump infusion method. 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. Male Albino Hartley guinea pigs (250-350 g). 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. 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.

Citations

Dec 26, 2012·Hearing Research·Hideto Fukui, Yehoash Raphael
Mar 6, 2012·Advanced Drug Delivery Reviews·Erin E Leary PararasJeffrey T Borenstein
Nov 16, 2010·International Journal of Pharmaceutics·Ya ZhangJing Zou
Jun 29, 2012·Gene Therapy·R SacheliB Malgrange
Aug 30, 2018·Physiological Reviews·Jing Wang, Jean-Luc Puel
Jan 3, 2019·Genomics & Informatics·Nathanial T Carpena, Min Young Lee
Sep 8, 2011·Current Opinion in Otolaryngology & Head and Neck Surgery·Ilmari PyykköYa Zhang
Jul 28, 2020·Journal of Clinical Medicine·Sedigheh Delmaghani, Aziz El-Amraoui
May 11, 2020·Advanced Drug Delivery Reviews·Ning DingXue Gao
Apr 6, 2021·Frontiers in Neuroscience·Ryan CraneMuna I Naash

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