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Intramuscular plasmid DNA injection can accelerate autoimmune responses.
G MacColl1, C Bunn, G Goldspink
1Department of Medicine, Royal Free and University College Medical School, London, UK.
Gene Therapy
|September 26, 2001
Summary
Repeated plasmid DNA injections in autoimmunity-prone mice significantly increased anti-double stranded DNA (dsDNA) and anti-nuclear autoantibodies. This suggests potential iatrogenic autoimmunity in susceptible individuals.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Gene therapy utilizes plasmid vectors for DNA delivery.
- Autoimmunity involves the immune system attacking self-antigens.
- Understanding potential immune side effects of gene delivery is crucial.
Purpose of the Study:
- To investigate if plasmid DNA administration induces autoantibody production.
- To assess the role of eukaryotic transcription factor binding sites in autoantibody formation.
- To evaluate responses in both normal and autoimmunity-prone mouse models.
Main Methods:
- Administration of plasmid vectors into mammalian muscle.
- Monitoring of anti-double stranded DNA (dsDNA) and anti-nuclear autoantibody levels.
- Comparison of immune responses in normal mice versus MRL/MpJ (autoimmunity-prone) mice.
Main Results:
- Normal mice showed no significant anti-DNA response after repeated plasmid DNA injections.
- Autoimmunity-prone MRL/MpJ mice exhibited a significant increase in anti-dsDNA and anti-nuclear antibodies.
- Eukaryotic transcription factor binding sites did not enhance autoantibody formation in normal mice.
Conclusions:
- Repeated administration of bacterial plasmids with eukaryotic promoter elements can induce immune responses.
- These responses may lead to antibodies cross-reacting with mammalian DNA and nuclear antigens.
- The potential for iatrogenic autoimmunity in susceptible individuals warrants consideration.