Nucleic acid constructs containing genes encoding transport...

Details Nucleic acid constructs containing genes encoding transport... Nucleic acid constructs containing genes encoding transport...

1997-05-02

2001-05-22

Schwartzman, Robert A. (Department: 1636)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C435S320100, C435S357000, C435S366000, C536S023100, C536S024100

Reexamination Certificate

active

06235526

ABSTRACT:

FIELD
The present application relates to nucleic acid constructs containing genes encoding transport signals, which can be used to manipulate the retention of transcription products in a cell's nucleus.
BACKGROUND
In gene therapy, genes are introduced into an organism for the purpose of expressing them in the organism. The regulation of the expression of these genes is important to the prophylactic or therapeutic effect of gene therapy.
Patent Applications PCT/GB95/02000, PCT/EP95/03370, PCT/EP95/03371, PCT/EP95/03368, PCT/EP95/03339 describe gene expression regulators. These regulators comprise an activator sequence whose function is, for example, the cell-specific or virus-specific activation of basal transcription. The DNA sequence of this activator sequence is linked, by its 3′ end, to the 5′ end of a promoter module. The structural gene is in turn linked, by its 5′ end, to the 3′ end of the promoter module.
The promoter module comprises nucleic acid sequences which bind to the transcription factors of the CDF and CHF or E2F and CHF families. In the G0 and G1 phases of the cell cycle, this binding leads to inhibition of the upstream activator sequence and consequently to inhibition of the transcription of the structural gene which is located downstream (i.e., in the direction of transcription).
In the G0 and G1 phases of cell division, the DNA contained in the cell is in the diploid state. The cell is at rest in the G0 phase and is inhibited in its cell-cycle progression in the G1 phase. The G1 phase is followed by the S phase, in which DNA synthesis takes place and in which the genome is replicated. There then follows the G2 phase, in which the cell is in the tetraploid state. The G2 phase is followed by cell division (mitosis or “M phase”). The daughter cells pass into the G0 or G1 states, and so on.
Consequently, combining a cell-specific or virus-specific activator sequence with a promoter module which inhibits this activator sequence in the G0 and G1 phases makes it possible to regulate the expression of a structural gene both in a cell-specific or virus-specific manner and in a cell-cycle-specific manner (i.e., restricted to the S and G2 phases).
The combination of an activator sequence and a promoter module is termed a “chimeric” promoter. While there are numerous possibilities for applying chimeric promoters in gene therapy, the shortcomings of these promoters also impose a number of limitations.
Examples of these limitations include:
a weak activator sequence, which leads to insufficient transcription of the structural gene,
the use of an activator sequence which cannot be adequately inhibited in a cell-cycle-dependent manner by the chosen promoter module,
the restriction to two (for example cell or virus-specific and cell-cycle-specific) regulators of the transcription of the structural gene, and
inadequate retention of the transcription product in the cell nucleus
and/or inadequate intracellular transport of the transcription product of the structural gene which has been introduced into the cell.
SUMMARY
It is an object of the present invention to make available nucleic acid constructs which make it possible to regulate the expression of foreign genes (transgenes) in a host cell in a more precise manner. The present invention relates, therefore, to nucleic acid constructs which possess a gene encoding a nuclear retention signal which is linked, downstream in the reading direction, to a transgene.


REFERENCES:
patent: 5464758 (1995-11-01), Gossen et al.
patent: 5604114 (1997-02-01), Haseltine et al.
patent: 5830880 (1998-11-01), Sedlacek et al.
patent: 5854019 (1998-12-01), Sedlacek et al.
patent: 5885833 (1999-03-01), Sedlacek et al.
patent: 5916803 (1999-06-01), Sedlacek et al.
patent: 0 464 633 A1 (1991-06-01), None
patent: 0 511 917 A1 (1992-04-01), None
patent: 92/21750 (1992-12-01), None
patent: 94/20621 (1994-09-01), None
patent: WO 95/21927 (1995-08-01), None
patent: WO 96/05994 (1996-02-01), None
patent: WO 96/06941 (1996-03-01), None
patent: WO 96/06938 (1996-03-01), None
patent: WO 96/06943 (1996-03-01), None
patent: WO 96/06940 (1996-03-01), None
patent: 96/09392 (1996-03-01), None
Bevec et al. (1994) Constitutive expression of chimeric Neo-rev response element transcripts suppresses HIV-1 replication in human CD4+ T lymphocytes. Human Gene Ther. 5:193-201, Feb. 1994.*
Zimmermann et al. (1992) Expression of chimeric Neo-rev response element sequences interferes with rev-dependent HIV-1 gag expression. Human Gene Ther. 3:155-161, Apr. 1992.*
Gazit et al. (1996) Two species of rev proteins, with distinct N termini, are expressed by caprine arthritis encephalitis virus. J. Virol. 70:2674-2677, Apr. 1996.*
W.M. Michael et al., “Signal Sequences that Target Nuclear Import and Nuclear Export of Pre-mRNA-binding Proteins”, Cold Spring Harbor Symposia on Quantitative biology, Bd. 60 Nr. 0, 1995, p. 663-68.
W. Michael et al., “A Nuclear Export Signal in hnRNP A1: A Signal-Mediated, Temperature-Dependent Nuclear Protein Export Pathway”, Cell, vol. 83, No. 1995, p. 415-422.
Junginger, H-E, et al., “Liposomen und Niosomen—Herstellung und Prüfung”, Jahrgang, pp. 1631-1641, 1991 (Abstract).
Nicholas B La Thangue, “DP and E2F proteins: components of a heterodimeric transcription factor implicated in cell cycle control”, Current Biology, pp. 443-450, 1994.
Lafage, M., et al., “The Human Interleukin-1&agr; Gene Is Located on the Long Arm of Chromosome 2 at Band q13”, Blood, vol. 73, No. 1, pp. 104-107, 1989.
Lage, A., et al., “H. pyloriVacuolating Toxin and Gastric Cancer”, Acta Gastro-Enterologica Belgica, p. 61, 1993.
Lemon, S.M., et al., “Genetic, antigenic and biological differences between strains of hepatitis A virus”, Vaccine, vol. 10, Suppl. 1, pp. S40-S44, 1992.
Leuther, K.K., et al., “Nondissociation of GAL4 and GAL80 in Vivo After Galactose Induction”, Science, vol. 256, pp. 1333-1335, 1992.
Levine, et al., “Live oral vaccines against cholera: an update”, Vaccine, vol. 11, Issue 2, pp. 207-212, 1993.
Lichtenstein, et al., “Definition and functional analysis of the signal/anchor domain of the human respiratory syncytial virus glycoprotein G”, J. of General Virology, vol. 77, pp. 109-118, 1996.
Maddon, et al., “The Isolation and Nucleotide Sequence of a cDNA Encoding the T Cell Surface Protein T4: A New Member of the Immunoglobulin Gene Family”, Cell, vol. 42, pp. 93-104, 1985.
Malim, et al., “The HIV-1 rev trans-activator acts through a structural target sequence to activate nuclear export of unspliced viral mRNA”, Nature, vol. 338, pp. 254-257 1989.
Malim, H.M., et al., “HIV-1 Structural Gene Expression Requires the Binding of Multiple Rev Monomers to the Viral RRE: Implications for HIV-1 Latency”, Cell, vol. 65, pp. 241-248, 1991.
Malim, M.H., et al., “Mutational Definition of the Human Immunodeficiency Virus Type 1 Rev Activation Domain”, J. of Virology, pp. 4248-4254, 1991.
Mandell, R. B., et al., “Identification of Two HSP70-related Xenopus Oocyte Proteins That Are Capable of Recycling Across the Nuclear Envelope”, J. of Cell Biol., vol. 111, pp. 1775-1783, 1990.
Mancuso, V.A., et al., “Posttranscriptional Effector Domains in the Rev Proteins of Feline Immunodeficiency Virus and Equine Infectious Anemia Virus”, J. of Virology, pp. 1998-2001, 1994.
Marasco, W.A., et al., “Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody”, Proc. Natl. Acad. Sci, USA, vol. 90, pp. 7889-7893, 1993.
March, C.J., et al., “Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs”, Nature, vol. 315, pp. 641-647, 1985.
Maruyama, K. et al., “Lipid composition is important for highly efficient target binding and retention of immunoliposomes”, Proc. Natl. Acad. Sci., USA, vol. 87, pp. 5744-5748, 1990.
Matsui, H., et al., “Molecular Cloning and Expression of the Human Interleukin 2 Gene” Lymphokines, vol. 12, pp. 1-12, 1985.
Maurice, J., “Malaria Vaccine Raises a Dilemma”, Science, vol. 267, pp. 320-323, 1995.
McBurney, M.W., et al., “The m

Affiliated with

Also associated with

Rating

Nucleic acid constructs containing genes encoding transport... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Nucleic acid constructs containing genes encoding transport..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid constructs containing genes encoding transport... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2451602