Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F23%3A00581769" target="_blank" >RIV/68378041:_____/23:00581769 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41434-022-00380-z" target="_blank" >https://www.nature.com/articles/s41434-022-00380-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41434-022-00380-z" target="_blank" >10.1038/s41434-022-00380-z</a>
Alternative languages
Result language
angličtina
Original language name
Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters
Original language description
Recombinant adeno-associated viral vectors (AAVs) are an effective system for gene transfer. AAV serotype 2 (AAV2) is commonly used to deliver transgenes to retinal ganglion cells (RGCs) via intravitreal injection. The AAV serotype however is not the only factor contributing to the effectiveness of gene therapies. Promoters influence the strength and cell-selectivity of transgene expression. This study compares five promoters designed to maximise AAV2 cargo space for gene delivery: chicken beta-actin (CBA), cytomegalovirus (CMV), short CMV early enhancer/chicken beta-actin/short beta-globulin intron (sCAG), mouse phosphoglycerate kinase (PGK), and human synapsin (SYN). The promoters driving enhanced green fluorescent protein (eGFP) were examined in adult C57BL/6J mice eyes and tissues of the visual system. eGFP expression was strongest in the retina, optic nerves and brain when driven by the sCAG and SYN promoters. CBA, CMV, and PGK had moderate expression by comparison. The SYN promoter had almost exclusive transgene expression in RGCs. The PGK promoter had predominant expression in both RGCs and AII amacrine cells. The ubiquitous CBA, CMV, and sCAG promoters expressed eGFP in a variety of cell types across multiple retinal layers including Muller glia and astrocytes. We also found that these promoters could transduce human retina ex vivo, although expression was predominantly in glial cells due to low RGC viability. Taken together, this promoter comparison study contributes to optimising AAV-mediated transduction in the retina, and could be valuable for research in ocular disorders, particularly those with large or complex genetic cargos.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/EF15_003%2F0000419" target="_blank" >EF15_003/0000419: Center of Reconstructive Neuroscience</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Gene Therapy
ISSN
0969-7128
e-ISSN
1476-5462
Volume of the periodical
30
Issue of the periodical within the volume
9
Country of publishing house
DE - GERMANY
Number of pages
17
Pages from-to
503-519
UT code for WoS article
000912984200001
EID of the result in the Scopus database
2-s2.0-85146186602