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. 1996 Jun 15;97(12):2911–2916. doi: 10.1172/JCI118750

Expression of naked DNA in human, pig, and mouse skin.

U R Hengge 1, P S Walker 1, J C Vogel 1
PMCID: PMC507388  PMID: 8675706

Abstract

The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epidermis, but also in the dermis and underlying fat and muscle tissue, and is expressed at lower levels. These findings suggest that genes can be expressed in human skin, after injection of naked DNA, and indicate that pig skin is an appropriate model for the study of DNA uptake and gene expression in human skin. The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained from patients with skin disease may be studied as skin grafts and organ cultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. G., Kamen B. A., Rothberg K. G., Lacey S. W. Potocytosis: sequestration and transport of small molecules by caveolae. Science. 1992 Jan 24;255(5043):410–411. doi: 10.1126/science.1310359. [DOI] [PubMed] [Google Scholar]
  2. Baron S., Dianzani F. The interferons: a biological system with therapeutic potential in viral infections. Antiviral Res. 1994 Jul;24(2-3):97–110. doi: 10.1016/0166-3542(94)90058-2. [DOI] [PubMed] [Google Scholar]
  3. Dowty M. E., Williams P., Zhang G., Hagstrom J. E., Wolff J. A. Plasmid DNA entry into postmitotic nuclei of primary rat myotubes. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4572–4576. doi: 10.1073/pnas.92.10.4572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hengge U. R., Chan E. F., Foster R. A., Walker P. S., Vogel J. C. Cytokine gene expression in epidermis with biological effects following injection of naked DNA. Nat Genet. 1995 Jun;10(2):161–166. doi: 10.1038/ng0695-161. [DOI] [PubMed] [Google Scholar]
  5. Hickman M. A., Malone R. W., Lehmann-Bruinsma K., Sih T. R., Knoell D., Szoka F. C., Walzem R., Carlson D. M., Powell J. S. Gene expression following direct injection of DNA into liver. Hum Gene Ther. 1994 Dec;5(12):1477–1483. doi: 10.1089/hum.1994.5.12-1477. [DOI] [PubMed] [Google Scholar]
  6. Jain V. K., Magrath I. T. A chemiluminescent assay for quantitation of beta-galactosidase in the femtogram range: application to quantitation of beta-galactosidase in lacZ-transfected cells. Anal Biochem. 1991 Nov 15;199(1):119–124. doi: 10.1016/0003-2697(91)90278-2. [DOI] [PubMed] [Google Scholar]
  7. Lane A. T., Scott G. A., Day K. H. Development of human fetal skin transplanted to the nude mouse. J Invest Dermatol. 1989 Dec;93(6):787–791. doi: 10.1111/1523-1747.ep12284423. [DOI] [PubMed] [Google Scholar]
  8. MacGregor G. R., Caskey C. T. Construction of plasmids that express E. coli beta-galactosidase in mammalian cells. Nucleic Acids Res. 1989 Mar 25;17(6):2365–2365. doi: 10.1093/nar/17.6.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pescovitz M. D., Hsu S. M., Katz S. I., Lunney J. K., Shimada S., Sachs D. H. Characterization of a porcine CD1-specific mAb that distinguishes CD4/CD8 double-positive thymic from peripheral T lymphocytes. Tissue Antigens. 1990 Apr;35(4):151–156. doi: 10.1111/j.1399-0039.1990.tb01772.x. [DOI] [PubMed] [Google Scholar]
  10. Raz E., Carson D. A., Parker S. E., Parr T. B., Abai A. M., Aichinger G., Gromkowski S. H., Singh M., Lew D., Yankauckas M. A. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9519–9523. doi: 10.1073/pnas.91.20.9519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sikes M. L., O'Malley B. W., Jr, Finegold M. J., Ledley F. D. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther. 1994 Jul;5(7):837–844. doi: 10.1089/hum.1994.5.7-837. [DOI] [PubMed] [Google Scholar]
  12. Wolff J. A., Ludtke J. J., Acsadi G., Williams P., Jani A. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet. 1992 Sep;1(6):363–369. doi: 10.1093/hmg/1.6.363. [DOI] [PubMed] [Google Scholar]
  13. Wolff J. A., Malone R. W., Williams P., Chong W., Acsadi G., Jani A., Felgner P. L. Direct gene transfer into mouse muscle in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
  14. Yovandich J., O'Malley B., Jr, Sikes M., Ledley F. D. Gene transfer to synovial cells by intra-articular administration of plasmid DNA. Hum Gene Ther. 1995 May;6(5):603–610. doi: 10.1089/hum.1995.6.5-603. [DOI] [PubMed] [Google Scholar]

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