Trans-ocular Electric Current In Vivo Enhances AAV-Mediated Retinal Gene Transduction after Intravitreal Vector Administration

Hongman Song, Ronald A. Bush, Yong Zeng, Haohua Qian, Zhijian Wu, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

Abstract

Adeno-associated virus (AAV) vector-mediated gene delivery is a promising approach for therapy, but implementation in the eye currently is hampered by the need for delivering the vector underneath the retina, using surgical application into the subretinal space. This limits the extent of the retina that is treated and may cause surgical injury. Vector delivery into the vitreous cavity would be preferable because it is surgically less invasive and would reach more of the retina. Unfortunately, most conventional, non-modified AAV vector serotypes penetrate the retina poorly from the vitreous; this limits efficient transduction and expression by target cells (retinal pigment epithelium and photoreceptors). We developed a method of applying a small and safe electric current across the intact eye in vivo for a brief period following intravitreal vector administration. This significantly improved AAV-mediated transduction of retinal cells in wild-type mice following intravitreal delivery, with gene expression in retinal pigment epithelium and photoreceptor cells. The low-level current had no adverse effects on retinal structure and function. This method should be generally applicable for other AAV serotypes and may have broad application in both basic research and clinical studies.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalMolecular Therapy - Methods and Clinical Development
Volume13
DOIs
StatePublished - Jun 14 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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