Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle
(2005) In Journal of Gene Medicine 7(2). p.218-227- Abstract
- Background Injection of DNA encoding exogenic proteins into muscle tissue combined with electroporation often results in a transient increase of the encoded protein concentration in the muscle and the blood. The reduction is normally due to an immune response against the exogenic protein but other factors may also be involved. How various electroporation parameters affect the concentration kinetics of syngenic and exogenic proteins is studied in relation to immune response and muscle damage after electroporation-mediated DNA transfer to muscle. Methods Electroporation was applied to mouse quadriceps muscles after injection of DNA encoding either secreted alkaline phosphatase (SEAP) or a mouse IgG molecule. Protein concentrations in blood... (More)
- Background Injection of DNA encoding exogenic proteins into muscle tissue combined with electroporation often results in a transient increase of the encoded protein concentration in the muscle and the blood. The reduction is normally due to an immune response against the exogenic protein but other factors may also be involved. How various electroporation parameters affect the concentration kinetics of syngenic and exogenic proteins is studied in relation to immune response and muscle damage after electroporation-mediated DNA transfer to muscle. Methods Electroporation was applied to mouse quadriceps muscles after injection of DNA encoding either secreted alkaline phosphatase (SEAP) or a mouse IgG molecule. Protein concentrations in blood or muscle and antibody responses were measured for a period up to 3 months. Tissue inflammation and muscle cell damage were studied on muscle cross-sections and assessed by measuring the concentrations of creatine phosphokinase (CPK) in blood. Results Mice with the highest SEAP concentration in blood at day 7 also had the highest rate of decrease afterwards, the strongest antibody responses against SEAP and the highest acute levels of CPK in blood. DNA-transfected muscle fibers were significantly reduced in number from days 7 to 14. Mononuclear cells surrounded the reporter gene expressing muscle fibers, thus indicating a cellular immune response. When using DNA encoding a syngenic protein the protein concentration in blood was relatively stabile over a 3-month period, but showed different kinetics for various electroporation parameters. Conclusions Our findings suggest that the optimal electroporation. parameters for DNA vaccination may be different from the optimal parameters for long-term expression of genes encoding syngenic proteins. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/251809
- author
- Gronevik, E ; Vult von Steyern, Fredrik LU ; Kalhovde, JM ; Tjelle, TE and Mathiesen, I
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- transfection, intramuscular injection, electroporation, electroporation parameters, gene therapy, DNA vaccination
- in
- Journal of Gene Medicine
- volume
- 7
- issue
- 2
- pages
- 218 - 227
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000227253900009
- pmid:15515140
- scopus:14844291308
- ISSN
- 1521-2254
- DOI
- 10.1002/jgm.650
- language
- English
- LU publication?
- yes
- id
- 91f5a353-bd90-4d86-af1d-effa198e13d5 (old id 251809)
- date added to LUP
- 2016-04-01 12:11:02
- date last changed
- 2022-01-26 23:58:40
@article{91f5a353-bd90-4d86-af1d-effa198e13d5,
abstract = {{Background Injection of DNA encoding exogenic proteins into muscle tissue combined with electroporation often results in a transient increase of the encoded protein concentration in the muscle and the blood. The reduction is normally due to an immune response against the exogenic protein but other factors may also be involved. How various electroporation parameters affect the concentration kinetics of syngenic and exogenic proteins is studied in relation to immune response and muscle damage after electroporation-mediated DNA transfer to muscle. Methods Electroporation was applied to mouse quadriceps muscles after injection of DNA encoding either secreted alkaline phosphatase (SEAP) or a mouse IgG molecule. Protein concentrations in blood or muscle and antibody responses were measured for a period up to 3 months. Tissue inflammation and muscle cell damage were studied on muscle cross-sections and assessed by measuring the concentrations of creatine phosphokinase (CPK) in blood. Results Mice with the highest SEAP concentration in blood at day 7 also had the highest rate of decrease afterwards, the strongest antibody responses against SEAP and the highest acute levels of CPK in blood. DNA-transfected muscle fibers were significantly reduced in number from days 7 to 14. Mononuclear cells surrounded the reporter gene expressing muscle fibers, thus indicating a cellular immune response. When using DNA encoding a syngenic protein the protein concentration in blood was relatively stabile over a 3-month period, but showed different kinetics for various electroporation parameters. Conclusions Our findings suggest that the optimal electroporation. parameters for DNA vaccination may be different from the optimal parameters for long-term expression of genes encoding syngenic proteins.}},
author = {{Gronevik, E and Vult von Steyern, Fredrik and Kalhovde, JM and Tjelle, TE and Mathiesen, I}},
issn = {{1521-2254}},
keywords = {{transfection; intramuscular injection; electroporation; electroporation parameters; gene therapy; DNA vaccination}},
language = {{eng}},
number = {{2}},
pages = {{218--227}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Gene Medicine}},
title = {{Gene expression and immune response kinetics using electroporation-mediated DNA delivery to muscle}},
url = {{http://dx.doi.org/10.1002/jgm.650}},
doi = {{10.1002/jgm.650}},
volume = {{7}},
year = {{2005}},
}