Inhibiting the growth p53 deficient tumor cells by administering

Details Inhibiting the growth p53 deficient tumor cells by administering Inhibiting the growth p53 deficient tumor cells by administering

1992-10-13

2000-01-25

Crouch, Deborah

Drug, bio-affecting and body treating compositions

Whole live micro-organism, cell, or virus containing

Genetically modified micro-organism, cell, or virus

514 44, 4351723, 4353201, 935 62, A61K 4800, C12N 1500

Patent

active

060175249

ABSTRACT:
Disclosed are methods and compositions for the selective manipulation of gene expression through the preparation of retroviral expression vectors for expressing antisense sequences, such as K-ras oncogene antisense sequences, or sequences encoding a desired product, such as wild type p53 sequences. Preferred retroviral vectors of the present invention incorporate the .beta.-actin promoter in a reverse orientation with respect to retroviral transcription. Preferred antisense RNA constructs of the present invention employ the use of antisense intron DNA corresponding to distinct intron regions of the gene whose expression is targeted for down-regulation. In an exemplary embodiment, a human lung cancer cell line (NCI-H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a genomic segment of K-ras in antisense orientation. Translation of the mutated K-ras mRNA was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A three-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA and cells remained viable. The growth of H460a tumors in nu
u mice was substantially reduced by expressed K-ras antisense RNA.

REFERENCES:
patent: 4740463 (1988-04-01), Weinberg et al.
patent: 4980289 (1990-12-01), Temin et al.
patent: 5055400 (1991-10-01), Lo et al.
Casey et al., "Growth Suppression of Human Breast Cancer Cells by the Introduction of a Wide-Type p53 Gene," Oncogene, 6:1791-1797, 1991.
Wills and Menzel, "Adenovirus Vectors for Gene Therapy of Cancer," Journal of Cellular Biochemistry, p. 204, Abstract # S216, Mar.-Apr. 1993.
Zhang et al., "Generation and Identification of Recombinant Adenovirus by Liposome-Mediated Transfection and PCR Analysis," BioTechniques, 15(5):868-872, 1993.
Bandyopadhyay & Temin, "Expression of Complete Chicken Thymidine Kinase Gene Inserted in a Tetrovirus Vector," Molecular and Cellular Biology, 4(4):749-754, 1984.
Bowtell et al., "Comparison of Expression in Hemopoietic Cells by Retroviral Vectors Carrying Two Genes," Journal of Virology, 62(7):2464-2473, 1988.
Casson et al., "p53 Gene Mutations in Barrett's Epithelium and Esophageal Cancer," Cancer Research, 51:4495-4499, 1991.
Chen et al., "Genetic Mechanisms of Tumor Suppression by the Human p53 Gene," Science, 250:1576-1580, 1990.
Chen et al., "Expression of Wild-Type p53 in Human A673 Cells Suppresses Tumorigenicity but Not Growth Rate," Oncogene, 6:1799-1805, 1991.
Goyette et al., "Progression of Colorectal Cancer Is Associated with Multiple Tumor Suppressor Gene Defects but Inhibition of Tumorigenicity Is Accomplished by Correction of Any Single Defect via Chromosome Transfer," Molecular and Cellular Biology, 12(3):1387-1395, 1992.
Gusterson et al., "Expression of p53 in Premalignant and Malignant Squamous Epithelium," Oncogene, 6:1785-1798, 1991.
Kumar et al., "Activation of ras Oncogenes Preceding the Onset of Neoplasia," Science, 248:1101-1104, 1990.
Maxwell et al., "Inefficiency of Expression of Luciferase Reporter from Transfected Murine Leukaemia Proviral DNA May Be Partially Overcome by Providing a Strong Polyadenylation Signal," Journal of General Virology, 72:1721-1724, 1991.
Mukhopadhyay et al., "Specific Inhibition of K-ras Expression and Tumorigenicity of Lung Cancer Cells by Antisense RNA," Cancer Research, 51:1744-1748, 1991.
Owens & Boyd, "Expressing Antisense Po RNA in Schwann Cells Perturbs Myelination," Development, 112:639-649, 1991.
Palmer et al., "Efficient Retrovirus-Mediated Transfer and Expression of a Human Adenosine Deaminase Gene in Diploid Skin Fibroblasts from an Adenosine Deaminase-Deficient Human," Proceedings of the National Academy of Science USA, 84:1055-1059, 1987.
Seyama et al., "In Vitro and In Vivo Regulation of Liver Epithelial Cells Carrying a Metallothionein-rasT24 Fusion Gene," Molecular Carcinogenesis, 1:89-95, 1988.
Takahashi et al., "Wild-Type but Not Mutant p53 Suppresses the Growth of Human Lung Cancer Cells Bearing Multiple Genetic Lesions," Cancer Research, 52:2340-2343, 1992.
Zhou & Duesberg, "myc Protooncogene Linked to Retroviral Promoter, but Not to Enhancer, Transforms Embryo Cells," Proceedings of the National Academy of Science USA, 85:2924-2928, 1988.
Conroy, "New Gene Therapy Cleared for Use Against Lung Cancer," Biotech Daily, pp. 3-4, Sep. 18, 1992.
Sundaresan, V., et al., "Somatic Genetic Changes in Pre-Invasive Lesions in Bronchial Epithelium," J. Pathol., 167(Suppl) 1992, 100A, Abstract Only.
Dialog Search Reports dated Aug. 7, 1992 and Feb. 26, 1993.
Kasid et al (1989) Science 243, 1354-1356.
Debus et al., J Cancer Res Clin Oncol, 116(Suppl Part 1):5-162, Abstract # A2.037.09, 1990.
Delauney et al., "A stable bifunctional antisense transcript inhibiting gene expression in transgenic plants", Proc. Natl. Acad. Sci. USA, 85:4300-4304, 1988.
Feig, et al., "Somatic Activation of ras.sup.K Gene in a Human Ovarian Carcinoma", Science, 223:698-701, 1984.
Finkel, et al., "Activation of ras Genes in Human Tumors Does Not Affect Localization, Modification, or Nucleotide Binding Properties of p21", Cell, 37:151-158, 1984.
Griep and Heiner, "Antisense Myc sequences induce differentiation of F9 cells", Proc. Natl. Acad. Sci. USA, 85:6806-6810, 1988.
Gunning, et al., "A human .beta.-actin expression vector system directs high-level accumulation of antisense transcripts", Proc. Natl. Acad. Sci. USA, 84:4831-4835, 1987.
Kasid, et al., "Effect of Antisense c-raf-1 on Tumorigenicity and Radiation Sensitivity of a Human Squamous Carcinoma", Science, 243:1354-1356, 1989.
Khokha, Rama, et al., "Antisense RNA-Induced Reduction in Murine TIMP Levels Confers Oncogenicity on Swiss 3T3 Cells", Science, 243:947-950, 1989.
Kris, et al, "Expression of Ki-Ras Oncogene in Tumor Cell Variants Exhibiting Different Metstatic Capabilities", Int. J. Cancer, 35:227-230, 1985.
Izant and Weintraub, "Inhibition of Thymidine Kinase Gene Expression by Anti-Sense RNA: A Molecular Approach to Genetic Analysis", Cells, 36:1007-1015, 1984.
Johnson, et al., "Transfection of a Rat Cell Line with the v-Ki-ras Onocogene is Associated with Enhanced Sussceptibility to Natural Killer Cell Lysis", J. Exp. Med., 162:1732-1737, 1985.
McGrath, et al., "Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene", Nature, 304:501, 1983.
Magrath, "Tumor-specific antisense oligonucleotides for controlling cancer", Abstract No. 114:55778n, Chemical Abstracts, 114(7):68 (1991).
Mercola, et al., "Antisense RNA: Eukaryotic Controls", Gene, 72:253-265 (1988).
Miller and Rosman, Improved Retroviral Vectors for Gene Transfer and Expression, BioTechniques, 7(9):980-990, 1989.
Munroe, Stephen H., "Antisense RNA inhibits splicing of pre-mRNA in vitro", The EMBO Journal, 7(8):2523-2532 (1988).
Prochownik, et al., "c-myc Antisense Transcripts Accelerate Differentiation and Inhibit G.sub.1 Progresion in Murine Erythroleukemia Cells", Molecular and Cellular Biology, 8(9):3683-3695, 1988.
Santos, et al., Malignant Activation of a K-ras Oncogene in Lung Carcinoma but Not in Normal Tissue of the Same Patient, Science, 223:661-664, 1984.
Shimizu, et al., "Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1", Nature, 304:497-500, 1983.
Stowers, et al., "Activation of the K-ras Protooncogene in Lung Tumors from Rats and Mice Chronically Exposed to Tetranitromethane", Cancer Research, 47:3212-3219, 1987.
Taya, et al., "A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer", The EMBO Journal, 3(12):2943-2946, 1984.
Toftgard, et al., "Proto-oncogene expression during two-stage carcinogenesis in mouse skin", Carcinogenesis, 6(4):655-657, 1985.
Vogelstein, et al., "Genetic Alterations Durin gColorectal-Tumor Development", The New England Journal of Medicine, 319(9):525-532, 1988.
Wahran et al., Tumour Biol, 6:41-56, 1985.
Winter and Perucho, "Oncogene Amplification during Tumorigenesis of Established Rat Fibroblasts Reversibly Transformed by

Affiliated with

Also associated with

Rating

Inhibiting the growth p53 deficient tumor cells by administering does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibiting the growth p53 deficient tumor cells by administering, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibiting the growth p53 deficient tumor cells by administering will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2313818