Gene delivery to cone photoreceptors by subretinal injection of rAAV2/6 in the mouse retina

Tesshu Hori; Masashi Fukutome; Chiseto Maejima; Hiroki Matsushima; Kensuke Kobayashi; Soichiro Kitazawa; Ryo Kitahara; Katsunori Kitano; Kenta Kobayashi; Satoru Moritoh; Chieko Koike

doi:10.1016/j.bbrc.2019.05.117

Gene delivery to cone photoreceptors by subretinal injection of rAAV2/6 in the mouse retina

Biochem Biophys Res Commun. 2019 Jul 12;515(1):222-227. doi: 10.1016/j.bbrc.2019.05.117. Epub 2019 May 27.

Authors

Affiliations

¹ Graduate School of Pharmacy, Ritsumeikan University, Kusatsu, Shiga, Japan; College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
² College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan; Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
³ College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
⁴ College of Information Science and Engineering, Ritsumeikan University, Kusatsu, Shiga, Japan; Center for Systems Vision Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan.
⁵ Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
⁶ College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan; Center for Systems Vision Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan.
⁷ College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan; Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan; Center for Systems Vision Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan. Electronic address: koike@fc.ritsumei.ac.jp.

PMID: 31146917
DOI: 10.1016/j.bbrc.2019.05.117

Abstract

Adeno-associated virus (AAV) has been studied as a safe delivery tool for gene therapy of retinal blinding diseases such as Leber's congenital amaurosis (LCA). The tropism of recombinant AAV (rAAV) including its specificity and efficiency in targeting retinal cell types has been studied with native or engineered capsids, along with specific promoters. However, one of the rAAV serotypes, rAAV2/6, has not been well-studied based on a report of low infection efficiency in the retina. We investigated the tropism of several rAAVs by subretinal injection in the adult mouse and found that rAAV2/6 predominantly infected cone photoreceptors including the main spectral type. Our data suggest that subretinal injection with rAAV2/6 may provide both an efficacious and specific means of gene delivery to cone photoreceptors in murine retinas.

Keywords: Adeno-associated virus; Cone photoreceptors; Gene therapy; The mammalian retina.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dependovirus / genetics*
Genetic Therapy / methods*
Genetic Vectors / administration & dosage
Genetic Vectors / genetics*
Injections
Leber Congenital Amaurosis / genetics
Leber Congenital Amaurosis / therapy
Mice, 129 Strain
Opsins / genetics
Opsins / metabolism
Retina / metabolism*
Retina / virology
Retinal Cone Photoreceptor Cells / metabolism*
Retinal Cone Photoreceptor Cells / virology
Retinal Diseases / genetics
Retinal Diseases / therapy*
Treatment Outcome

Substances

Opsins