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Electroporation of Plasmid DNA into Mouse Skeletal Muscle
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DNA Electrotransfer Regulates Molecular Functions in Skeletal Muscle.

Amanda Sales Conniff1, Jared Tur1, Kristopher Kohena1

  • 1Department of Medical Engineering, University of South Florida, Tampa, Florida, USA.

Bioelectricity
|August 9, 2024
PubMed
Summary
This summary is machine-generated.

Electric pulses enhance plasmid DNA delivery to muscle tissue, causing specific molecular changes related to stress and inflammation. Understanding these effects is key for developing effective gene therapies.

Keywords:
RNA sequencingelectroporationelectrotransfermolecular functionsplasmidskeletal muscle

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Area of Science:

  • Molecular biology
  • Genetics
  • Biotechnology

Background:

  • Skeletal muscle is a target for plasmid DNA (pDNA) delivery for vaccines and therapeutics.
  • Electroporation (electric pulses) enhances cell permeability for improved pDNA delivery and expression.
  • Molecular effects of DNA electrotransfer on muscle tissue are not well understood.

Purpose of the Study:

  • To characterize the molecular changes in muscle tissue following intramuscular DNA electrotransfer.
  • To differentiate the effects of electric pulses versus pDNA injection on gene expression.
  • To identify unique molecular responses to guide gene therapy development.

Main Methods:

  • Intramuscular pDNA electrotransfer in muscle tissue.
  • RNA sequencing to evaluate gene expression changes four hours post-treatment.
  • Gene Ontology (GO) pathway enrichment analysis of differentially expressed genes.

Main Results:

  • GO analysis revealed enriched functions related to muscle stress, cytoskeleton, and inflammation from pulse application.
  • pDNA injection regulated terms associated with DNA-directed responses and control.
  • pDNA electrotransfer affected pathways similar to pulse application, but also included pDNA entry and trafficking.

Conclusions:

  • Muscle stimulus via DNA electrotransfer induces specific molecular functions.
  • Identifying these intrinsic molecular changes is crucial for designing effective gene therapies.