Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1994-04-26
1996-12-24
Martinell, James
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435 695, 435 6951, 435 6952, 4351723, 4352402, 4353201, C12P 2100, C12P 2102, C12N 1500, C12N 1506
Patent
active
055873006
ABSTRACT:
The present invention provides a method to increase the production of a regulatory molecule, i.e., a molecule that regulates cell behavior, such as a cytokine or a protooncogene, in a population of transfected cells, whether normal (resting or activated) or tumor cells. The method involves mutating a native or "wild type" cDNA sequence that encodes an mRNA sequence for a regulatory molecule to form a mutant cDNA sequence capable of producing a more stable mRNA sequence. Specifically, the method involves mutating a wild type cDNA sequence that encodes an unstable mRNA sequence for the regulatory molecule, wherein the mRNA includes a 3' untranslated region having a destabilizing element comprising an AUUUA sequence, to form a mutant cDNA sequence capable of producing a more stable mRNA sequence, wherein the AUUUA sequence is replaced by AUGUA, AUAUA, GUGUG, AGGGA, GAGAG, or a combination thereof; and transfecting a cell population with the mutant cDNA sequence so that the production of the regulatory molecule is enhanced by the cells.
REFERENCES:
T. Aharon et al., "Selective Destabilization of Short-Lived mRNAs with the Granulocyte-Macrophage Colony-Stimulating Factor AU-Rich 3' Noncoding Region Is Mediated by a Cotranslational Mechanism", Molecular and Cellular Biology, 13(3), 1971-1980 (1993).
J. K. Burkholder et al., "Rapid transgene expression in lymphocyte and macrophage primary cultures after particle bombardment-mediated gene transfer", J. Immunol. Methods., 165, 149-156 (1993).
P. Gillis et al., "The Adenosine-Uridine Binding Factor Recognizes the AU-rich Elements of Cytokine, Lymphokine, and Oncogene mRNAs", J. Biol. Chem., 266(5), 3172-3177 (1991).
R. Higuchi, "Using PCR to Engineer DNA in PCR Technology": H. Erlich, Ed.; Stockton Press, New York, NY; 61-70 (1989), Chapter 6.
C. O. Jacob et al., "Disruption in the AU motif of the mouse TNF-.alpha. 3'UTR correlates with reduced TNF production by macrophages in vitro", Nucleic Acids Research, 21(11), 2761-2766 (1993).
T. R. Jones, et al., "Rapid Cytoplasmic Turnover of c-myc mRNA: Requirement of the 3' Untranslated Sequences", Molecular and Cellular Biology, 7(12), 4513-4521 (1987).
J. S. Malter, "Identification of an AUUUA-Specific Messenger RNA Binding Protein", Science, 246, 664-666 (1989).
J. S. Malter, et al., "A Redox Switch and Phosphorylation Are Involved in the Post-translational Up-regulation of the Adenosine-Uridine Binding Factor by Phorbol Ester and Ionophore", J. Biol. Chem., 266 (5), 3167-3171 (1991).
J. S. Malter et al., "Adenosine-Uridine Binding Factor Requires Metals for Binding to Granulocyte-Macrophage Colony-Stimulating Factor mRNA", Enzyme, 44, 203-213 (1990).
J. S. Malter, Abstract of National Institute of Health Grant No. 5R01DK45213. This Abstract was obtained from the online DIALOG file Federal Research in Progress.
F. Meijlink, "Removal of a 67-base-pair sequence in the Noncoding region of protooncogene fos converts it to a transforming gene", Proc. Natl. Acad. Sci. USA, 82, 4987-4991 (1985).
T. Otsuka et al., "Isolation and Characterization of an Expressible cDNA Encoding Human IL-3 ", J. Immunol., 140, 2288-2295 (1988).
I. J. Rondon et al., "Hypoxia Up-regulates the Activity of a Novel Erythropoietin mRNA Binding Protein", J. Biol. Chem., 266 (25), 16594-16598 (1991).
S. Savant-Bhonsale et al., "Evidence for instability of mRNAs containing AUUUA motifs mediated through translation-dependent assembly of a >20S degradation complex", Genes & Development, 6, 1927-1939 (1992).
G. D. Schuler et al., "GM-CSF and Oncogene mRNA Stabilities Are Independently Regulated in trans in a Mouse Monocytic Tumor", Cell, 55, 1115-1122 (1988).
G. Shaw et al., "A Conserved AU Sequence from the 3'Untranslated Region of GM-CSF mRNA Mediates Selective mRNA Degradation", Cell, 46, 659-667 (1986).
J. M. Stephens et al., "Tumor Necrosis Factor .alpha.-induced Glucose Transporter (GLUT-1) mRNA Stabilization in 3T3-L1 Preadipocytes", J. Biol. Chem., 267(12), 8336-8341 (1992).
A. Wodnar-Filipowicz et al., "Regulation of interleukin 3mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions", Proc. Natl. Acad. Sci. USA, 87, 777-781 (1990).
M. Akashi et al., "Number and Location of AUUUA Motifs: Role in Regulating Transiently Expressed RNAs," Blood, 83, 3182-3187 (Jun. 1, 1994).
T. Wilson et al., "Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences," Nature, 336, 396-399 (Nov. 1988).
Martinell James
Wisconsin Ulumni Research Foundation
LandOfFree
Method to increase regulatory molecule production does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method to increase regulatory molecule production, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method to increase regulatory molecule production will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1178109