861 results about "Over expression" patented technology

The present invention relates to the construction and engineering of cells, more particularly microorganisms for producing PUFAs with four or more double bonds from non-fatty acid substrates through heterologous expression of an oxygen requiring pathway. The invention especially involves improvement of the PUFA content in the host organism through fermentation optimization, e.g. decreasing the temperature and / or designing an optimal medium, or through improving the flux towards fatty acids by metabolic engineering, e.g. through over-expression of fatty acid synthases, over-expression of other enzymes involved in biosynthesis of the precursors for PUFAs, or codon optimization of the heterologous genes, or expression of heterologous enzymes involved in the biosynthesis of the precursor for PUFAs.

Compositions and methods for treatment of conditions related to the overexpression of EZH2, such as late stage prostate cancer, using a DNA methylation inhibitor and / or a histone deacetylase inhibitor, optionally in combination with an EZH2 antagonist and / or an antineoplastic agent, to specifically target diseases associated with EZH2 over-expression. Further provided are reagents and kits for treatment of EZH2 overexpression.

An extremoyzme over-expression system in which Pseudomonads and closely related bacteria are used as host cells, and methods and kits for use thereof, extremozymes expressed therefrom.

The present invention relates to a fungal C16 / 18 fatty acid elongase that is able to catalyze the conversion of palmitate (16:0) to stearic acid (18:0). Specifically, the nucleotide sequence of a Mortierella alpina C16 / 18 fatty acid elongase is provided (designated as “ELO3”). Methods of increasing microbial oil production, increasing carbon flux into the polyunsaturated fatty acid biosynthetic pathway and increasing the content of polyunsaturated fatty acids by over-expression of the C16 / 18 fatty acid elongase are described herein. Most desirably, the substrate specificity of the instant ELO3 will be particularly useful to enable accumulation of long-chain polyunsaturated fatty acids in oleaginous yeast, such as Yarrowia lipolytica.

Disclosed are 2-methoxy antimycin derivatives or analogs that modulate apoptosis by binding to the hydrophobic groove of a Bcl-2 family member protein (e.g., Bcl-2 or BCl-xL). The 2-methoxy antimycin derivatives or analogs are used in disclosed methods for treating apoptosis-associated diseases such as, for example, neoplastic disease (e.g., cancer) or other proliferative diseases associated with the over-expression of a Bcl-2 family member protein.

Disclosed herein are methods and sequences to preferentially suppress the expression of the mutated huntingtin (“htt”) protein over expression of the normal htt protein. Also disclosed are methods comprising screening an individual for the heterozygous presence of one or more single nucleotide polymorphisms within the individual's Huntington's genes; administering nucleic acid molecules comprising nucleotide sequences that preferentially suppress the expression of amino acid sequences encoding for mutated huntingtin (“htt”) over suppressing the expression of amino acid sequences encoding for normal htt by targeting an area of a Huntington's disease gene that is heterozygous for the presence of one or more single nucleotide polymorphisms.

The present invention relates to a fungal C16 / 18 fatty acid elongase that is able to catalyze the conversion of palmitate (16:0) to stearic acid (18:0). Specifically, the nucleotide sequence of a Mortierella alpina C16 / 18 fatty acid elongase is provided (designated as “ELO3”). Methods of increasing microbial oil production, increasing carbon flux into the polyunsaturated fatty acid biosynthetic pathway and increasing the content of polyunsaturated fatty acids by over-expression of the C16 / 18 fatty acid elongase are described herein. Most desirably, the substrate specificity of the instant ELO3 will be particularly useful to enable accumulation of long-chain polyunsaturated fatty acids in oleaginous yeast, such as Yarrowia lipolytica.

The present invention provides a method for treating wounds and diseases in mammals, caused by mammalian cells involved in an inflammatory response, by altering indigenous in vivo levels of peroxynitrous acid, and salts thereof. The method comprises contacting the mammalian cells with a therapeutically effective amount of a reactive oxygen species mediator, wherein the reactive oxygen species mediator is selected from the group consisting of pyruvates, pyruvate precursors, α-keto acids having four or more carbon atoms, precursors of α-keto acids having four or more carbon atoms, and the salts thereof, wherein mediation of reactive oxygen species results in mediation of peroxynitrous acid. The present invention further provides a pharmaceutical composition for treating wounds and diseases in mammals, caused by mammalian cells involved in an inflammatory response, by altering indigenous in vivo levels of peroxynitrous acid, and salts thereof.

The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

The present invention relates, in part, to the discovery that human FGF19 is amplified in a number of cancers, including liver and esophageal cancers, and that this amplification correlates with over-expression of this gene. In some aspects, the invention provides methods and kits for diagnosing a patient having or at risk for developing cancer, such as liver or esophageal cancer. The invention in other aspects provides methods for selecting a treatment for a patient having cancer. In other aspects, the invention relates to methods for treating cancer using an FGF19 inhibitor.

The invention provides a humanized PD-L1 tumor cell line MC-38-hPD-L1, a builtanimal tumor model with the same and a method for constructing the humanized PD-L1 tumor cell line. The method particularly includes knocking out animal-origin PD-L1 by the aid of CRISPR-CAS9; carrying out amplification and cultivation to obtain knocked-out cell banks; extracting DNA (deoxyribonucleic acid) and carrying out PCR (polymerase chain reaction) amplification; recycling and cloning amplification products; carrying out over-expression on human-origin PD-L1 in MC-38 cell lines of mPD-L1 KO by the aid of lentivirus systems; packaging lentivirus and screening Puromycin to obtain the humanized MC-38 cell line of PD-L1. The humanized PD-L1 tumor cell line, the animal tumor model and the method have the advantages that as shown by results, high killing efficiency and multiplication capacity are obviously presented by tumor infiltration CD8 T lymphocytes after antibody treatment is carried out, tumor infiltration Treg cells can be obviously inhibited after antibody treatment is carried out, and accordingly the method is proved to be effective and feasible from the aspect of molecular mechanisms.

The invention provides application of a tobacco NtNAC096 gene in control tobacco aging, belonging to the field of tobacco biological control. The tobacco NtNAC096 gene can be used for regulating and controlling the aging of tobaccos significantly. The full length of a DNA sequence of a genome using the tobacco NtNAC096 gene c is 1203bp, and the genome consists of 3 exons and 2 introns. The application specifically comprises the following steps: (1) cloning the tobacco NtNAC096 gene, and performing sequence analysis; (2) performing expression analysis on the NtNAC096 gene; (3) performing function analysis on the tobacco NtNAC096 gene by establishing an over-expression vector of the tobacco NtNAC096 gene; and (4) designing target sites of the tobacco NtNAC096 gene by using a CRISPR / Cas9 gene editing technology, establishing a NtNAC096 gene knockout vector, and performing genetic transformation on a tobacco variety, thereby obtaining a tobacco plant capable of delaying aging.

A non-human animal model is provided, particularly a mouse model for movement hyperactivity, excitoxicity disorders (e.g. myoclonic cramping) and neurodegeneration, in which modified cytoplasmic dynein heavy chain1 is expressed. Modified human and mouse cytoplasmic dynein heavy chain1 proteins and nucleic adds are also provided, including the corresponding recombinant proteins. The invention further provides uses for the non-human animal model and the modified cytoplasmic dynein heavy chain1 proteins and nucleic acids, in particular for the diagnosis and treatment of medical conditions associated with over-expression of cytoplasmic dynein heavy chain1.

The invention discloses an EGFR inhibitor. The EGFR inhibitor is of the structure shown in the formula (I) and is a compound including alpha, beta-unsaturated carboxylic acid amides. Meanwhile, the invention discloses a preparing method of the compound and the application of the compound serving as a protein tyrosine kinase inhibitor, especially the inhibiting function on T790M variant EGFR as the EGFR inhibitor, and the application on treating diseases such as the kidney cancer, the ling cancer, the prostate cancer, the pancreatic cancer the breast cancer and the spongiocytoma which are related to EGFR over expression. The structure is shown in the specification.

The invention discloses a saccharomyces cerevisiae strain with high yield of ester and low yield of higher alcohol as well as a building method of the saccharomyces cerevisiae strain, and belongs to the technical field of bioengineering. According to the building method provided by the invention, through completely knocking out an amino acid transaminase gene BAT2 and an ester hydrolase gene IAH1 in an original strain, and selecting a strong promoter PGK1 over-expression alcohol acetyltransferase I gene ATF1 at the same time, the saccharomyces cerevisiae strain with high yield of ester and low yield of higher alcohol is obtained. Compared with a parent strain, other fermentation performances of built recombinant bacteria are not affected, the total quantity of acetic acid ester is obviously increased and reaches 1303.6mg / L, wherein the content of ethyl acetate is 52 times that of the original strain, isoamyl acetate is increased to 73.7mg / L, the content of main higher alcohol is 151.8mg / L and is reduced by 61.4 percent in comparison with that of the original strain. By using the saccharomyces cerevisiae, ester yield is significantly increased while the higher alcohol yield is reduced, the higher requirements of white spirit related fields on yeast are met and the application prospect is wide.

The invention discloses a thermo-sensitive male fertility gene and an application thereof and also discloses a genetic marker of the thermo-sensitive male fertility gene, and provides a protein coded by the thermo-sensitive male fertility gene and a carrier containing the thermo-sensitive male fertility gene and a recombinant microorganism. The invention also discloses the application of the thermo-sensitive male fertility gene in cultivating a thermo-sensitive male sterile line and an application of the genetic marker in rice breeding. The thermo-sensitive fertility gene TSSNR is acquired through the map-based cloning technique of Annong S-1 thermo-sensitive sterility gene locus tms5, functions of the gene are validated through transgene experiments, and the transgene technique of RNAi or antisense RNA or the over-expression dominant negative principle is provided, functions of the TSSRZ gene in normal rice varieties are incapable, so as to cultivate the thermo-sensitive male sterile line, and the application value is significant.

Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over- expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.

The present invention relates to fungal Δ12 fatty acid desaturases that are able to catalyze the conversion of oleic acid to linoleic acid (LA; 18:2). Nucleic acid sequences encoding the desaturases, nucleic acid sequences which hybridize thereto, DNA constructs comprising the desaturase genes, and recombinant host microorganisms expressing increased levels of the desaturases are described. Methods of increasing production of specific ω-3 and ω-6 fatty acids by over-expression of the Δ12 fatty acid desaturases are also described herein.

A synergistically effective combination of an anti-cancer agent and a therapeutic compound, such as an mTOR-Rictor complex inhibitor, a Serine 473 phosphorylation inhibitor, an AKT2 inhibitor, or a combination thereof, for use in the treatment of cancer, and methods and uses thereof. Also included are methods and uses of a thiosemicarbazone for treating a cancer in a mammal in need thereof characterized by over-expression of RAS, by an EGFR mutation, and / or by over-expression of AKT2.

The present invention discloses a RGD-labeled fluorescent gold nano-cluster preparation method, which comprises: preparing gold nanoparticles with a particle size of less than 2 nm by using a BSA method; and carrying out an amidation reaction on the prepared gold nano-cluster and RGD having amino to obtain the RGD-labeled fluorescent gold nano-clusters. According to the present invention, the obtained gold nano-cluster (Au Nanoclusters, AuNCs) is the novel precious metal fluorescent nanometer material, and has characteristics of simple preparation conditions, simple preparation steps, near-infrared light emitting under a visible light source, small particle size, good monodispersity, good stability, low toxic-side effect, high safety, stable fluorescent property, and high CT imaging contrast resolution; a small amount of expression of integrin [alpha]v[beat]3 exists in most normal tissues and mature vascular endothelial cells while the over-expression of the integrin [alpha]v[beat]3 exists in a variety of cancer cells and neovessel endothelial cells, and the ligand is called RGD polypeptide sequence; and the RGD is selected as the targeting molecule, and the AuNCs and the RGD polypeptide sequence are conjugated to prepare the RGD-labeled fluorescent gold nano-cluster RGD-AuNCs@BSA.

Disclosed herein are methods and sequences to preferentially suppress the expression of the mutated huntingtin (“htt”) protein over expression of the normal htt protein. Also disclosed are methods comprising screening an individual for the heterozygous presence of one or more single nucleotide polymorphisms within the individual's Huntington's genes; administering nucleic acid molecules comprising nucleotide sequences that preferentially suppress the expression of amino acid sequences encoding for mutated huntingtin (“htt”) over suppressing the expression of amino acid sequences encoding for normal htt by targeting an area of a Huntington's disease gene that is heterozygous for the presence of one or more single nucleotide polymorphisms.

The invention relates to the field of genetic engineering, and in particular relates to an anti-EGFR ((Epidermal Growth Factor Receptor) chimeric antigen receptor, and a lymphocyte for expressing the antigen receptor. The technical solution of the invention provides a new effective selection for the anti-tumor technical field. The technical scheme is that a single-chain antibody targeting the EGFR is provided. The single-chain antibody is further designed to be constructed into the chimeric antigen receptor by means of a genetic engineering technology, and the structure of the gained chimeric antigen receptor is anti-EGFR (scFv)-IgG2 (Fc)-CD28-CD3 Zeta. According to the genetically engineered lymphocyte targeting the human EGFR, the chimeric antigen receptor is transfected into the lymphocyte by the nucleofaction technology, and thus the nonspecific lymphocyte can be endowed with the capacity of specifically distinguishing the EGFR tumor antigen and targeting and killing the EGFR over-expression tumor cells. According to the technical scheme, the adoptive cell therapy and the genetic therapy are organically combined, so that remarkable effect of killing the tumor is gained, and a novel effective selection is provided for the field.

Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.

The invention relates to the technical field of plant genetic engineering, in particular relates to isolating clone and functional verification of a DAN fragment containing a gene OsWRKY45-2 related to rice disease resistance. The gene OsWRKY45-2 codes WRKY proteinoids and can endow rice with resistance to the diseases caused by bacterial pathogenic bacteria, namely the leaf blight bacteria (Xanthomonas oryzae pv.oryzae) and fungal pathogenic bacteria, namely the rice blast bacteria (Magnaporthe grisea). The fragment and the exogenous regulatory sequence thereof are directly transferred into rice, thus the resistance capability of transgenic rice with over-expression OsWRKY45-2 against bacterial blight in and rice blast is improved remarkably.

The invention relates to an improved glutathione production method. Recombination strain capable of efficiently conversing L-cysteine, L-glutamic acid and glycine into glutathione can be obtained by screening of recombinant expression host and selection of appropriate enzyme for over expression, and the recombination strain can effectively improve the yield of GSH(glutathione). The method can increase the yield of GSH by more than 50%.

The present disclosure relates to methods for the early detection of ERG over-expression, gene rearrangements, and diagnosis and / or prognosis of prostate cancer using a combined ERG IHC-FISH assay.

Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.

The present invention relates to a method for analyzing differential gene expression associated with breast tumor, based on the analysis of the over-expression or under-expression of polynucleotide sequences in a biological sample. The analysis comprises the detection of the over-expression of at least one polynucleotide sequence(s), subsequence(s) or complement(s) thereof selected from predefined polynucleotide sequence sets.