Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 116, Issue 6, Pages 979-982Publisher
BLACKWELL SCIENCE INC
DOI: 10.1046/j.1523-1747.2001.01341.x
Keywords
direct injection; dissemination; expression; plasmid
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Gene therapy using naked DNA injected into muscle and skin is increasingly being used for vaccination and treatment purposes. Favorably, naked plasmid DNA does not exhibit the various limitations inherent to viral vectors, such as the elicitation of adverse immune responses and the risk of insertional mutagenesis. In order to assess the distribution and safety of naked plasmid DNA in a relevant animal model, we analyzed if intracutaneously injected plasmid DNA was transported to other organs and if ectopic expression occurred. When a superdose of a marker plasmid was injected intradermally, most organs were found transiently to contain the plasmid DNA for several days, whereas integration into the host genome was not detected. With the exception of ovary, however, mRNA expression only occurred in the skin, regional lymph nodes, and muscular tissues. From a safety standpoint, skin gene therapy with naked plasmid DNA can be considered safe due to the rapid biodegradation of plasmid DNA and the exclusive and transient expression of foreign genes in tissues known to take up DNA.
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