Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Pharmacological enhancement of in vivo foreign gene expression in muscle. Gene Ther 1994 Mar;1(2):114-21

Date

03/01/1994

Pubmed ID

7584066

Abstract

Intramuscular injection of naked plasmid DNA provides a means for gene transfer and expression in striated muscle. In this study, the effects of treating muscle with normal saline, etidocaine, mepivacaine, acetic anhydride, sodium bicarbonate, Notechis scutatus venom, cardiotoxin and bupivacaine before plasmid DNA injection on foreign gene expression were evaluated. Dose dependence, strain and species specificity, the time interval between pharmacological agent and plasmid DNA injection, the stability of gene expression and the fate of the injected plasmid DNA were studied using reporter gene expression, by histological examination and semi-quantitative polymerase chain reaction. Of the various agents tested, the best enhancement of foreign gene expression occurred in muscle treated with 0.75% bupivacaine five to seven days before plasmid DNA injection. Rat and mouse quadriceps muscle treated with 0.75% bupivacaine had levels of luciferase activity four- to 40-times greater than non-bupivacaine-treated muscle. Also, beta-galactosidase expressing myofibers were observed throughout the length of the muscle in samples treated with 0.75% bupivacaine before reporter gene injection. Muscle treated with 0.75% bupivacaine fully recovered from the degeneration caused by its injection with no long-term effects histologically. The heightened level of reporter gene expression persisted in 0.75% bupivacaine-treated muscle for one month, but decreased to that of non-bupivacaine-treated muscle by two months after plasmid DNA injection. Enhancement of foreign gene expression may be particularly advantageous in vaccination protocols employing intramuscular plasmid injection.

Author List

Danko I, Fritz JD, Jiao S, Hogan K, Latendresse JS, Wolff JA

Author

Jeffery Duane Fritz PhD Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetic Anhydrides
Animals
Bupivacaine
Cobra Cardiotoxin Proteins
Elapid Venoms
Etidocaine
Gene Expression
Gene Transfer Techniques
Genes, Reporter
Injections, Intramuscular
Luciferases
Mepivacaine
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred ICR
Muscle, Skeletal
Plasmids
Rats
Rats, Sprague-Dawley
Sodium Bicarbonate
beta-Galactosidase