Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of...
Patent
1997-08-01
1999-12-07
Campell, Bruce R.
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
514 44, 424 9321, 536 231, 435 691, 4353201, 435455, C12N 1500
Patent
active
059982055
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention generally relates to targeted gene therapy using recombinant vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional vectors and methods for using them. Such vectors are able to selectively replicate in a target tissue to provide a therapeutic benefit from the presence of the vector per se or from heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits transcription of the gene by means of the transcriptional regulatory sequence. With this vector, therefore, a target tissue can be selectively treated. The invention also relates to methods of using the vectors to screen a tissue for the presence or absence of transcriptional regulator functions that pen-nit vector replication by means of the transcriptional regulatory sequence. The invention also relates to cells for producing recombinant replication-conditional vectors useful for targeted gene therapy.
2. Background Art
Targeting Vectors
One of the major goals for therapeutic use of exogenous genes has been cell targeting with high specificity. General approaches have included systemic introduction of DNA, DNA-protein complexes, and liposomes. In situ administration of retroviruses has also been used for cells that are actively. replicating.
However, because of the lack of, or significantly low, cell-specificity and inefficient gene transfer, the targeting of desired genes to specific cells in an organism has been a major obstacle for exogenous gene-based therapy. Thus, the use of such genes has been limited.
Tumor cells are among those cell types for which it would be especially desirable to provide a means for exogenous gene targeting. In an embodiment of the present invention, compositions and methods are provided to deliver exogenous genes to tumor cells safely and efficiently.
Adenoviruses Generally
Adenoviruses are nonenveloped, regular icosohedrons. The protein coat (capsid) is composed of 252 capsomeres of which 240 are hexons and 12 are pentons. Most of the detailed structural studies of the adenovirus polypeptides have been done for adenovirus types 2 and 5. The viral DNA is 23.85.times.10.sup.6 daltons for adenovirus 2 and varies slightly in size depending on serotype. The DNA has inverted terminal repeats and the length of these varies with the serotype.
The replicative cycle is divided into early (E) and late (L) phases. The late phase defines the onset of viral DNA replication. Adenovirus structural proteins are generally synthesized during the late phase. Following adenovirus infection, host DNA and protein synthesis is inhibited in cells infected with most serotypes. The adenovirus lytic cycle with adenovirus 2 and adenovirus 5 is very efficient and results in approximately. 10,000 virions per infected cell along with the synthesis of excess viral protein and DNA that is not incorporated into the virion. Early adenovirus transcription is a complicated sequence of interrelated biochemical events, but it entails essentially the synthesis of viral RNAs prior to the onset of viral DNA replication.
The organization of the adenovirus genome is similar in all of the adenovirus groups and specific functions are generally positioned at identical locations for each serotype studied. Early cytoplasmic messenger RNAs are complementary to four defined, noncontiguous regions on the viral DNA. These regions are designated (E1-E4). The early transcripts have been classified into an array of immediate early (E1a), delayed early (E1b, E2a, E2b, E3 and E4), and intermediate (IVa2.1X) regions.
The E1a region is involved in transcriptional transactivation of viral and cellular genes as well as transcriptional repression of other
REFERENCES:
patent: 5416017 (1995-05-01), Burton et al.
patent: 5436146 (1995-07-01), Shenk et al.
patent: 5585096 (1996-12-01), Martuza et al.
patent: 5698443 (1997-12-01), Henderson et al.
patent: 5728379 (1998-03-01), Martuza et al.
patent: 5747469 (1998-05-01), Roth et al.
patent: 5804407 (1998-09-01), Tamaoki et al.
Vile et al. (Molecular Medicine Today, vol. 4, 2:84-92, 1998).
Russel (European Journal of Cancer, vol. 30A, 8:1165-1171, Aug. 1994).
Smith et al. (Human Gene Therapy, 5:29-35, 1994).
Abe, M., and Kufe, D., "Characterization of cis-acting elements regulating transcription of the human DF3 breast carcinoma-associated antigen (MUC1) gene," Proc. Natl. Acad. Sci. USA 90:282-286 (Jan. 1993).
Grooteclaes, M., et al., "The 6-Kilobase c-erbB2 Promoter Contains Positive and Negative Regulatory Elements Functional in Humn Mammary Cell Lines," Cancer Res., 54:4193-4199 (Aug. 1994).
Kovarik, A., et al., "Analysis of the Tissue-specific Promoter of the MUC1 Gene," J. Biol. Chem. 268:9917-9926 (May 1993).
Max-Audit, I., et al., "Transcriptional Regulation of the Pyruvate Kinase Erythroid-specific Promoter," J. Biol. Chem. 268:5431-5437 (Mar. 1993).
Morishita, K., et al., "A Novel Promoter for Vascular Endothelial Growth Factor Receptor (flt-1) That Confers Endothelial-specific Gene Expression," J. Biol. Chem. 270:27948-27953 (Nov. 1995).
Nakabayashi, H., et al., "A Position-Dependent Silencer Plays a Major Role in Repressing .alpha.-Fetoprotein Expression in Human Hepatoma," Mol. Cell. Biol. 11:5885-5893 (Dec. 1991).
Pang, S.,e t al., "Prostate Tissue Specificity of the Prostate-Specific Antigen Promoter Isolated from a Patient with Prostate Cancer," Human Gene Therapy 6:1417-1426 (Nov. 1995).
Richards, C.A., et al., "Transcriptional Regulatory Sequences of Carcinomembryonic Antigen: Identification and Use with Cytosine Deaminase for Tumor-Specific Gene Therapy," Human Gene Therapy 6:881-893 (Jul. 1995).
Babiss, L.E. et al., "Cellular Promoters Incorporated inot the Adenovirsu Genome: Effect of Viral DNA Replication on Endogenous and Exogenous Gene Transcription," J. Mol. Biol. 193:643-650 (1987).
Blaese, R.M. et al., "In Situ Delivery of Suicide Genes for Cancer Treatment," Eur. J. Cancer 30A(8):1190-1193 (Aug. 1994).
Brown, D., "Gene Therapy `Oversold` by Researchers, Journalists," The Washington Post, p. A22, Dec. 8, 1995.
Chellappan, S. et al., "Adenovirus E14, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product," Proc. Natl. Acad. Sci. USA 89:4549-4553 (1992).
Chen, S.-H. et al., "Gene therapy for brain tumors: Regression of experimental gliomas by adenovirus-mediated gene transfer in vivo," Proc. Natl. Acad. Sci. USA 91:3054-3057 (Apr. 1994).
Coghlan, A., "Gene dream fades away," New Scientist 145:14-15 (Nov. 1995).
Cornelis, J.J. et al., "Transformation of Human Fibroblasts by Ionizing Radiation, a Chemical Carcinogen, or Simian Virus 40 Correlates with an Increase in Susceptibility to the Autonomous Paroviruses H-1 Virus and Minute Virus of Mice," J. Virol. 62(5):1679-1686 (1988).
Crystal, R.G., "Transfer of Genes to Humans: Early Lessons and Obstacles to Success," Science 270:404-410 (Oct. 1995).
Culver, K.W. et al., "In Vivo Gene Transfer with Retroviral Vector-Producer Cells for Treatment of Experimental Brain Tumors," Science 256:1550-1552 (1992).
Dillon, N., "Regulating gene expression in gene therapy," Tibtech 11:167-173 (May 1993).
Dooley, T.P. et al., "Transactivation of the adenovirus Ella promoter in the absence of adenovirus E1A protein is restricted to mouse oocytes and preimplantation embryos," Development 107:945-956 (1989).
Dynan, W.S., "Modularity in Promoters and Enhancers," Cell 58:1-4 (1989).
Fattaey, A. et al., "Replication of Adenovirus Mutants in Human Cancer Cells," Astracts of papers presented at the 1994 meeting on Molecular Biology of Papovaviruses and Adenovruses, Aug. 17-Aug. 21, 1994, Col
Chang Yung-Nien
Chiang Yawen L.
Hallenbeck Paul L.
Campell Bruce R.
Genetic Therapy, Inc.
Nguyen Dave Trong
LandOfFree
Vectors for tissue-specific replication does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vectors for tissue-specific replication, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vectors for tissue-specific replication will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-822760