Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice.
Journal
Gene therapy
ISSN: 1476-5462
Titre abrégé: Gene Ther
Pays: England
ID NLM: 9421525
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
28
07
2019
accepted:
27
03
2020
revised:
19
03
2020
pubmed:
22
4
2020
medline:
19
8
2021
entrez:
22
4
2020
Statut:
ppublish
Résumé
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron (SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15 in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15 via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15 cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15 to severe Taiwanese Smn
Identifiants
pubmed: 32313099
doi: 10.1038/s41434-020-0146-8
pii: 10.1038/s41434-020-0146-8
pmc: PMC7674152
doi:
Substances chimiques
KLF15 protein, human
0
Klf15 protein, mouse
0
Kruppel-Like Transcription Factors
0
Survival of Motor Neuron 1 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
505-515Subventions
Organisme : Medical Research Council
ID : MR/R025312/1
Pays : United Kingdom
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