Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F18%3A00499613" target="_blank" >RIV/67985904:_____/18:00499613 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1089/hum.2017.199" target="_blank" >http://dx.doi.org/10.1089/hum.2017.199</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/hum.2017.199" target="_blank" >10.1089/hum.2017.199</a>
Alternative languages
Result language
angličtina
Original language name
Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease
Original language description
Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety in larger animals is lacking. HD transgenic sheep express the full-length human HTT with 73 CAG repeats. AAV9 was used to deliver unilaterally to HD sheep striatum an artificial miRNA targeting exon 48 of the human HTT mRNA under control of two alternative promoters: U6 or CA. The treatment reduced human mutant (m) HTT mRNA and protein 50-80% in the striatum at 1 and 6 months post injection. Silencing was detectable in both the caudate and putamen. Levels of endogenous sheep HTT protein were not affected. There was no significant loss of neurons labeled by DARPP32 or NeuN at 6 months after treatment, and Iba1-positive microglia were detected at control levels. It is concluded that safe and effective silencing of human mHTT protein can be achieved and sustained in a large-animal brain by direct delivery of an AAV carrying an artificial miRNA.
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
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Gene Therapy
ISSN
1043-0342
e-ISSN
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Volume of the periodical
29
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
663-673
UT code for WoS article
000426036100001
EID of the result in the Scopus database
2-s2.0-85044582983