Abstract
Retroviral vectors are the most efficient tool for stably introducing genes into vertebrate cells. However, their use is limited by the host range of the retrovirus from which they are derived. To alter the host range, we recently constructed retrovirus vector particles, derived from spleen necrosis virus, that display a single-chain antigen-binding site of an antibody (scA) on the viral surface (T.-H. T. Chu, I. Martinez, W. Sheay, and R. Dornburg, Gene Ther. 1:292-299, 1994). Using a hapten (2,4-dinitrophenol) model system, we showed that such particles are competent for infection. In this study, we repeated our experiments using an scA directed against a cell surface protein expressed on various human carcinoma cell lines. We found that such scA-displaying particles can efficiently infect human cells that express the corresponding antigen. Particles with wild-type spleen necrosis virus envelope are minimally infectious on such cells. The addition of the original monoclonal antibody to the viral vector particle solution prior to infection inhibited infection. This competition assay showed that the infection is mediated by the antibody moiety and, therefore, is antibody specific. These data indicate that retroviral vectors with antibody-envelope fusion proteins may be a valuable tool for selectively introducing genes into any target cell.
Full Text
The Full Text of this article is available as a PDF (206.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bird R. E., Hardman K. D., Jacobson J. W., Johnson S., Kaufman B. M., Lee S. M., Lee T., Pope S. H., Riordan G. S., Whitlow M. Single-chain antigen-binding proteins. Science. 1988 Oct 21;242(4877):423–426. doi: 10.1126/science.3140379. [DOI] [PubMed] [Google Scholar]
- Casella C. R., Panganiban A. T. The matrix region is responsible for the differential ability of two retroviruses to function as helpers for vector propagation. Virology. 1993 Feb;192(2):458–464. doi: 10.1006/viro.1993.1061. [DOI] [PubMed] [Google Scholar]
- Chu T. H., Martinez I., Sheay W. C., Dornburg R. Cell targeting with retroviral vector particles containing antibody-envelope fusion proteins. Gene Ther. 1994 Sep;1(5):292–299. [PubMed] [Google Scholar]
- Colcher D., Bird R., Roselli M., Hardman K. D., Johnson S., Pope S., Dodd S. W., Pantoliano M. W., Milenic D. E., Schlom J. In vivo tumor targeting of a recombinant single-chain antigen-binding protein. J Natl Cancer Inst. 1990 Jul 18;82(14):1191–1197. doi: 10.1093/jnci/82.14.1191. [DOI] [PubMed] [Google Scholar]
- Cournoyer D., Caskey C. T. Gene therapy of the immune system. Annu Rev Immunol. 1993;11:297–329. doi: 10.1146/annurev.iy.11.040193.001501. [DOI] [PubMed] [Google Scholar]
- Delwart E. L., Panganiban A. T. Role of reticuloendotheliosis virus envelope glycoprotein in superinfection interference. J Virol. 1989 Jan;63(1):273–280. doi: 10.1128/jvi.63.1.273-280.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilboa E. Retroviral gene transfer: applications to human therapy. Prog Clin Biol Res. 1990;352:301–311. [PubMed] [Google Scholar]
- Hunter E., Swanstrom R. Retrovirus envelope glycoproteins. Curr Top Microbiol Immunol. 1990;157:187–253. doi: 10.1007/978-3-642-75218-6_7. [DOI] [PubMed] [Google Scholar]
- Jorgensen R. A., Rothstein S. J., Reznikoff W. S. A restriction enzyme cleavage map of Tn5 and location of a region encoding neomycin resistance. Mol Gen Genet. 1979;177(1):65–72. doi: 10.1007/BF00267254. [DOI] [PubMed] [Google Scholar]
- Kewalramani V. N., Panganiban A. T., Emerman M. Spleen necrosis virus, an avian immunosuppressive retrovirus, shares a receptor with the type D simian retroviruses. J Virol. 1992 May;66(5):3026–3031. doi: 10.1128/jvi.66.5.3026-3031.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohn D. B., Anderson W. F., Blaese R. M. Gene therapy for genetic diseases. Cancer Invest. 1989;7(2):179–192. doi: 10.3109/07357908909038283. [DOI] [PubMed] [Google Scholar]
- Koo H. M., Brown A. M., Ron Y., Dougherty J. P. Spleen necrosis virus, an avian retrovirus, can infect primate cells. J Virol. 1991 Sep;65(9):4769–4776. doi: 10.1128/jvi.65.9.4769-4776.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koo H. M., Gu J., Varela-Echavarria A., Ron Y., Dougherty J. P. Reticuloendotheliosis type C and primate type D oncoretroviruses are members of the same receptor interference group. J Virol. 1992 Jun;66(6):3448–3454. doi: 10.1128/jvi.66.6.3448-3454.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mikawa T., Fischman D. A., Dougherty J. P., Brown A. M. In vivo analysis of a new lacZ retrovirus vector suitable for cell lineage marking in avian and other species. Exp Cell Res. 1991 Aug;195(2):516–523. doi: 10.1016/0014-4827(91)90404-i. [DOI] [PubMed] [Google Scholar]
- Miller A. D. Retrovirus packaging cells. Hum Gene Ther. 1990 Spring;1(1):5–14. doi: 10.1089/hum.1990.1.1-5. [DOI] [PubMed] [Google Scholar]
- Morgan R. A., Anderson W. F. Human gene therapy. Annu Rev Biochem. 1993;62:191–217. doi: 10.1146/annurev.bi.62.070193.001203. [DOI] [PubMed] [Google Scholar]
- Russell S. J., Hawkins R. E., Winter G. Retroviral vectors displaying functional antibody fragments. Nucleic Acids Res. 1993 Mar 11;21(5):1081–1085. doi: 10.1093/nar/21.5.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheay W., Nelson S., Martinez I., Chu T. H., Bhatia S., Dornburg R. Downstream insertion of the adenovirus tripartite leader sequence enhances expression in universal eukaryotic vectors. Biotechniques. 1993 Nov;15(5):856–862. [PubMed] [Google Scholar]