Details:

Alternative Title:
EMBO Mol Med
Publisher's site:
http://dx.doi.org/10.15252/emmm.201404077
Personal Author:
Cronin, Therese ; Vandenberghe, Luk H ; Hantz, Péter ; Juttner, Josephine ; Reimann, Andreas ; ... More +
Cronin, Therese ; Vandenberghe, Luk H ; Hantz, Péter ; Juttner, Josephine ; Reimann, Andreas ; Kacsó, Ágota–Enikő ; Huckfeldt, Rachel M ; Busskamp, Volker ; Kohler, Hubertus ; Lagali, Pamela S ; Roska, Botond ; Bennett, Jean ; Less -
Description:
In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (~100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use.
Subject:
[+]
Adeno-associated Virus
Animals
Capsid Library
Dependovirus
Genetic Vectors
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Multi-electrode Array
Mutagenesis, Site-Directed
Optogenetics
Promoter Optimization
Promoter Regions, Genetic
Research Articles
Retinal Bipolar Cells
Transduction, Genetic

Source:
EMBO Mol Med. 2014 ; 6(9):1175-1190.;
Pubmed ID:
25092770
Pubmed Central ID:
PMC4197864
Document Type:
Journal Article ;
Funding:
1R24EY019861‐01A1/EY/NEI NIH HHS/United States ; 8DP1 EY023177/DP/NCCDPHP CDC HHS/United States ; DP1 EY023177/EY/NEI NIH HHS/United States ; DP1 OD008267/OD/NIH HHS/United States ; R24 EY019861/EY/NEI NIH HHS/United States ;
1R24EY019861‐01A1/EY/NEI NIH HHS/United States ; 8DP1 EY023177/DP/NCCDPHP CDC HHS/United States ; DP1 EY023177/EY/NEI NIH HHS/United States ; DP1 OD008267/OD/NIH HHS/United States ; R24 EY019861/EY/NEI NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:ac9cce2113f7c2c5d3500d6230acd10e0725d45e82765355571bf0ba56a556cb
File Type:

Supporting Files

• 	emmm0006-1175-SD1.pdf	pdf
  	emmm0006-1175-SD2.pdf	pdf
  	emmm0006-1175-SD3.pdf	pdf
  	emmm0006-1175.nxml	txt
  	license.txt	txt
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