Transcriptomic Analysis of the Acute Skeletal Muscle Effects after Intramuscular DNA Electroporation Reveals Inflammatory Signaling.
RNA sequencing
plasmid electroporation
signaling pathways
skeletal muscle
Journal
Vaccines
ISSN: 2076-393X
Titre abrégé: Vaccines (Basel)
Pays: Switzerland
ID NLM: 101629355
Informations de publication
Date de publication:
29 Nov 2022
29 Nov 2022
Historique:
received:
07
11
2022
revised:
23
11
2022
accepted:
25
11
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Skeletal muscle is a promising tissue for therapeutic gene delivery because it is highly vascularized, accessible, and capable of synthesizing protein for therapies or vaccines. The application of electric pulses (electroporation) enhances plasmid DNA delivery and expression by increasing membrane permeability. Four hours after plasmid electroporation, we evaluated acute gene and protein expression changes in mouse skeletal muscle to identify regulated genes and genetic pathways. RNA sequencing followed by functional annotation was used to evaluate differentially expressed mRNAs. Our data highlighted immune signaling pathways that may influence the effectiveness of DNA electroporation. Cytokine and chemokine protein levels in muscle lysates revealed the upregulation of a subset of inflammatory proteins and confirmed the RNA sequencing analysis. Several regulated DNA-specific pattern recognition receptor mRNAs were also detected. Identifying unique molecular changes in the muscle will facilitate a better understanding of the underlying molecular mechanisms and the development of safety biomarkers and novel strategies to improve skeletal muscle targeted gene therapy.
Identifiants
pubmed: 36560447
pii: vaccines10122037
doi: 10.3390/vaccines10122037
pmc: PMC9786673
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA196796
Pays : United States
Organisme : US National Institutes of Health
ID : R01CA196796
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