The Retroviral Life Cycle and the Molecular Construction of Retrovirus Vectors
The discovery of a filterable agent that allowed the transmission of cancers in chickens (1) was the first identification of the viruses now known as retroviruses. Subsequently, genes transmitted by some retroviruses were identified as transforming oncogenes. These findings suggested that retroviruses may be used as genetic vectors, since retroviral oncogenes (v-onc) are altered forms of “highjacked” normal cellular genes (2), and the retroviruses that transform cells in culture are often defective for replication because the v-onc genes have been substituted in place of one or more of the essential replicative genes (3). Such defective oncogenic retroviruses can be propagated only in the presence of a wild-type “helper” virus, which supplies the functional gene products of the virus. Retroviruses can now be modified to become vehicles for the delivery and expression of cloned genes into a wide variety of cells, for both experimental and therapeutic purposes.
KeywordsGenomic Transcript Minus Strand Internal Promoter Producer Cell Line Vector Genome
- 5.Gluzman, Y. and Hughes, S. H. (1988) Viral Vectors (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY).Google Scholar
- 7.Varmus, H. E. (1983) Retroviruses, in Mobile Genetic Elements. (Shapiro, J., ed), Academic, NY, pp. 411–503.Google Scholar
- 10.Weiss, R. A., Teich, N., Varmus, J, and Coffin, J., eds. (1982,1985) Molecular Biology of Tumor Viruses, RNA Tumor Viruses (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY), vols. 1, 2.Google Scholar
- 14.Keller, G., Paige, P., Gilboa, E., and Wagner, E. F. (1985) Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature 318, 149–154.Google Scholar
- 24.Von Melchner, H. and Ruley, H. E. (1989) Identification of cellular promoters by using a retrovirus promoter trap. J. Virol 63, 3227–3233.Google Scholar