Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 15;90(10):4455–4459. doi: 10.1073/pnas.90.10.4455

In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment.

L Cheng 1, P R Ziegelhoffer 1, N S Yang 1
PMCID: PMC46530  PMID: 8506285

Abstract

The particle bombardment method of gene transfer provides an alternative approach for analysis of in vivo promoter activity and transgene expression. Transient expression of the firefly luciferase gene from five viral and five cellular promoters was assessed after in vivo gene transfer using this method. The relative strengths of these promoters were quantitatively determined in five different rat tissues: skin epidermis, dermis, muscle, liver, and pancreas. Cytomegalovirus immediate early enhancer/promoter activity was consistently the highest in each tissue, whereas other promoters displayed tissue-specific preferences. In liver, the mouse phosphoenolpyruvate carboxykinase and metallothionein promoters were stimulated in vivo by inducing agents at 1 and 5 days posttransfection. In dermis, sustained luciferase activity was observed for over 1.5 years after gene delivery. In vivo transgene expression was also detected in bombarded mouse, rabbit, and rhesus monkey tissues. These results suggest that particle bombardment provides an effective system for studies of in vivo gene transfer and gene therapy.

Full text

PDF
4455

Images in this article

Selected References

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

  1. Acsadi G., Jiao S. S., Jani A., Duke D., Williams P., Chong W., Wolff J. A. Direct gene transfer and expression into rat heart in vivo. New Biol. 1991 Jan;3(1):71–81. [PubMed] [Google Scholar]
  2. Anderson W. F. Human gene therapy. Science. 1992 May 8;256(5058):808–813. doi: 10.1126/science.1589762. [DOI] [PubMed] [Google Scholar]
  3. Furth P. A., Hennighausen L., Baker C., Beatty B., Woychick R. The variability in activity of the universally expressed human cytomegalovirus immediate early gene 1 enhancer/promoter in transgenic mice. Nucleic Acids Res. 1991 Nov 25;19(22):6205–6208. doi: 10.1093/nar/19.22.6205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hanahan D. Transgenic mice as probes into complex systems. Science. 1989 Dec 8;246(4935):1265–1275. doi: 10.1126/science.2686032. [DOI] [PubMed] [Google Scholar]
  5. Hatzoglou M., Bosch F., Park E. A., Hanson R. W. Hormonal control of interacting promoters introduced into cells by retroviruses. J Biol Chem. 1991 May 5;266(13):8416–8425. [PubMed] [Google Scholar]
  6. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  7. Jaenisch R. Transgenic animals. Science. 1988 Jun 10;240(4858):1468–1474. doi: 10.1126/science.3287623. [DOI] [PubMed] [Google Scholar]
  8. McGrane M. M., de Vente J., Yun J., Bloom J., Park E., Wynshaw-Boris A., Wagner T., Rottman F. M., Hanson R. W. Tissue-specific expression and dietary regulation of a chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice. J Biol Chem. 1988 Aug 15;263(23):11443–11451. [PubMed] [Google Scholar]
  9. Miller A. D. Human gene therapy comes of age. Nature. 1992 Jun 11;357(6378):455–460. doi: 10.1038/357455a0. [DOI] [PubMed] [Google Scholar]
  10. Oellig C., Seliger B. Gene transfer into brain tumor cell lines: reporter gene expression using various cellular and viral promoters. J Neurosci Res. 1990 Jul;26(3):390–396. doi: 10.1002/jnr.490260317. [DOI] [PubMed] [Google Scholar]
  11. Ponder K. P., Dunbar R. P., Wilson D. R., Darlington G. J., Woo S. L. Evaluation of relative promoter strength in primary hepatocytes using optimized lipofection. Hum Gene Ther. 1991 Spring;2(1):41–52. doi: 10.1089/hum.1991.2.1-41. [DOI] [PubMed] [Google Scholar]
  12. Scharfmann R., Axelrod J. H., Verma I. M. Long-term in vivo expression of retrovirus-mediated gene transfer in mouse fibroblast implants. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4626–4630. doi: 10.1073/pnas.88.11.4626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Selden R. F., Howie K. B., Rowe M. E., Goodman H. M., Moore D. D. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. doi: 10.1128/mcb.6.9.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Silva M. C., Wong D. W., Batt C. A. Cloning and partial nucleotide sequence of the genomic bovine beta-lactoglobulin gene. Nucleic Acids Res. 1990 May 25;18(10):3051–3051. doi: 10.1093/nar/18.10.3051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Thompson T. A., Gould M. N., Burkholder J. K., Yang N. S. Transient promoter activity in primary rat mammary epithelial cells evaluated using particle bombardment gene transfer. In Vitro Cell Dev Biol. 1993 Feb;29A(2):165–170. doi: 10.1007/BF02630949. [DOI] [PubMed] [Google Scholar]
  16. Williams R. S., Johnston S. A., Riedy M., DeVit M. J., McElligott S. G., Sanford J. C. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2726–2730. doi: 10.1073/pnas.88.7.2726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wolf J. B., David V. A., Deutch A. H. Identification of a distal regulatory element in the 5' flanking region of the bovine prolactin gene. Nucleic Acids Res. 1990 Aug 25;18(16):4905–4912. [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Wynshaw-Boris A., Short J. M., Loose D. S., Hanson R. W. Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. I. Multiple hormone regulatory elements and the effects of enhancers. J Biol Chem. 1986 Jul 25;261(21):9714–9720. [PubMed] [Google Scholar]
  20. Yang N. S., Burkholder J., Roberts B., Martinell B., McCabe D. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9568–9572. doi: 10.1073/pnas.87.24.9568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yang N. S. Gene transfer into mammalian somatic cells in vivo. Crit Rev Biotechnol. 1992;12(4):335–356. doi: 10.3109/07388559209040627. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES