Abstract
Background. Topical application is emerging as a new route of gene delivery. However, the extent of skin permeation and the in vivo fate of topically applied plasmid DNA are not fully understood. Methods. In vitro permeation of plasmid DNA across human skin and keratinocyte layers was tested using Franz diffusion cells. In vivo absorption and biodistribution of topically applied plasmid in mice were determined using quantitative polymerase chain reaction (PCR). The expression levels of plasmid DNA in various tissues were measured by semiquantitative reverse transcription PCR. Results. In vitro, topically applied DNA was capable of penetrating human skin and keratinocyte layers. Following topical application of plasmid DNA onto murine skin, the levels of plasmid DNA in the serum peaked at 4 hr. At 24 hr post-dose, topically applied DNA existed at higher levels than intravenously administered DNA in almost all tissues, and induced 11.4- and 22-fold higher mRNA expression in muscle and skin, respectively. Moreover, the topical route showed sustained expression of plasmid DNA in the regional lymph nodes over 5 days, whereas the intravenous route did not. Conclusions. Taken together, our results show that topically applied plasmid DNA is capable of permeating the skin and being expressed for prolonged periods in various tissues including lymph nodes. This suggests that skin may provide an appealing, noninvasive route of delivery for DNA vaccines and other therapeutic genes.
| Original language | English |
|---|---|
| Pages (from-to) | 1238-1246 |
| Number of pages | 9 |
| Journal | Journal of Gene Medicine |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2004 Nov 1 |
| Externally published | Yes |
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Keywords
- Expression
- Lymph nodes
- Permeation
- Plasmid DNA
- Topical application
ASJC Scopus subject areas
- Genetics
Cite this
Skin permeation, biodistribution, and expression of topically applied plasmid DNA. / Kang, Min Jeong; Kim, Chong Kook; Kim, Mi Young; Hwang, Tae Sun; Kang, Sang Yoon; Kim, Won-Ki; Ko, Jung Jae; Oh, Yu Kyoung.
In: Journal of Gene Medicine, Vol. 6, No. 11, 01.11.2004, p. 1238-1246.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skin permeation, biodistribution, and expression of topically applied plasmid DNA
AU - Kang, Min Jeong
AU - Kim, Chong Kook
AU - Kim, Mi Young
AU - Hwang, Tae Sun
AU - Kang, Sang Yoon
AU - Kim, Won-Ki
AU - Ko, Jung Jae
AU - Oh, Yu Kyoung
PY - 2004/11/1
Y1 - 2004/11/1
N2 - Background. Topical application is emerging as a new route of gene delivery. However, the extent of skin permeation and the in vivo fate of topically applied plasmid DNA are not fully understood. Methods. In vitro permeation of plasmid DNA across human skin and keratinocyte layers was tested using Franz diffusion cells. In vivo absorption and biodistribution of topically applied plasmid in mice were determined using quantitative polymerase chain reaction (PCR). The expression levels of plasmid DNA in various tissues were measured by semiquantitative reverse transcription PCR. Results. In vitro, topically applied DNA was capable of penetrating human skin and keratinocyte layers. Following topical application of plasmid DNA onto murine skin, the levels of plasmid DNA in the serum peaked at 4 hr. At 24 hr post-dose, topically applied DNA existed at higher levels than intravenously administered DNA in almost all tissues, and induced 11.4- and 22-fold higher mRNA expression in muscle and skin, respectively. Moreover, the topical route showed sustained expression of plasmid DNA in the regional lymph nodes over 5 days, whereas the intravenous route did not. Conclusions. Taken together, our results show that topically applied plasmid DNA is capable of permeating the skin and being expressed for prolonged periods in various tissues including lymph nodes. This suggests that skin may provide an appealing, noninvasive route of delivery for DNA vaccines and other therapeutic genes.
AB - Background. Topical application is emerging as a new route of gene delivery. However, the extent of skin permeation and the in vivo fate of topically applied plasmid DNA are not fully understood. Methods. In vitro permeation of plasmid DNA across human skin and keratinocyte layers was tested using Franz diffusion cells. In vivo absorption and biodistribution of topically applied plasmid in mice were determined using quantitative polymerase chain reaction (PCR). The expression levels of plasmid DNA in various tissues were measured by semiquantitative reverse transcription PCR. Results. In vitro, topically applied DNA was capable of penetrating human skin and keratinocyte layers. Following topical application of plasmid DNA onto murine skin, the levels of plasmid DNA in the serum peaked at 4 hr. At 24 hr post-dose, topically applied DNA existed at higher levels than intravenously administered DNA in almost all tissues, and induced 11.4- and 22-fold higher mRNA expression in muscle and skin, respectively. Moreover, the topical route showed sustained expression of plasmid DNA in the regional lymph nodes over 5 days, whereas the intravenous route did not. Conclusions. Taken together, our results show that topically applied plasmid DNA is capable of permeating the skin and being expressed for prolonged periods in various tissues including lymph nodes. This suggests that skin may provide an appealing, noninvasive route of delivery for DNA vaccines and other therapeutic genes.
KW - Expression
KW - Lymph nodes
KW - Permeation
KW - Plasmid DNA
KW - Topical application
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UR - http://www.scopus.com/inward/citedby.url?scp=13644257864&partnerID=8YFLogxK
U2 - 10.1002/jgm.620
DO - 10.1002/jgm.620
M3 - Article
VL - 6
SP - 1238
EP - 1246
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
SN - 1099-498X
IS - 11
ER -