17 results about "Transcriptional repression" patented technology

The present invention relates generally to compositions, systems and methods for modulating hepatitis B virus (HBV) by targeting gene repression. In particular, the present invention provides an epigenetically modified DNA targeting system, such as a CRISPR-Cas / guide RNA (gRNA) system, for transcriptional repression of hepatitis B virus genes to promote cell phenotypes that lead to reduced HBV infection. In some embodiments, the epigenetically modified DNA targeting systems of the present invention bind to or target a target site of at least one gene in the hepatitis B virus DNA sequence or a regulatory element thereof in a cell. In some aspects, the systems provided herein relate to transcriptional repression of one or more hepatitis B virus genes and / or regulatory elements thereof. In some aspects, the invention also provides methods and uses associated with the provided compositions, such as in repression of hepatitis B virus replication and expression associated with hepatitis B infection.

The application discloses high-temperature-resistant engineered methanotrophs with high glutamic acid yield, a construction method and application thereof, and belongs to the field of industrial biotechnology. Methylotuvimicrobium buryatense 5GB1 as the host strain, transcriptional inhibition of the SOS response system by LexA protein is removed by knocking out a lexA gene in the genome of the host strain, expression of DNA damage repair related genes in the cell is activated, and high-temperature-resistant engineered methanotrophs MBΔ lexA that can stably grow in a high-temperature environment of 40-45 DEG C are obtained. The strain can still maintain normal growth and metabolism with methane as the sole carbon source under the condition of 40-45 DEG C, and the glutamic acid synthesis capacity of the strain is significantly better than that of the original strain at normal temperature. The high-temperature-resistant engineered methanotrophs MBΔ lexA provide important strain resources for the production of amino acid products by methanotroph cell factories in a high-temperature industrial scene, and are expected to improve the economy and sustainability of methanotrophic bioconversion.

This invention belongs to the field of plant molecular biology and genetic breeding technology, specifically relating to a molecular marker related to the malic acid content of apple fruit and its application. The molecular marker is... MdNAC029 The single nucleotide polymorphism site in the gene promoter region, this site is located MdNAC029 The nucleotide sequence of the gene promoter region, starting from the 2693rd base at the 5' end, corresponds to... MdNAC029 At a position 442 bp upstream of the transcription start codon, the polymorphism is either T or C, with the C / C genotype indicating high malic acid content and the T / T genotype indicating low malic acid content. This invention, through molecular biology experiments, confirms that the T allele is the binding site for the transcriptional repressor MdMYC2, and the C allele eliminates the binding of MdMYC2, thereby relieving transcriptional repression and promoting malic acid accumulation. This provides a new molecular marker for the genetic improvement of apple fruit acidity traits, accelerating the breeding process of superior varieties.

According to the application of the rosiglitazone in preparation of the medicine for treating the glioma and the composition of the rosiglitazone, a brand-new Rb-E2F1-mediated MND1 transcription inhibition mechanism of the rosiglitazone in the glioma is clarified for the first time; and a new strategy with a great transformation prospect is provided for treatment of glioma, namely, a clinical drug rosiglitazone which has been subjected to security certification is utilized to interfere DNA repair steady state of glioma cells through targeted inhibition of MND1, so that tumor growth is inhibited.

Provided is an epigenetic editor comprising a transcriptional activator-like effector (TALE) domain, at least one epigenetic modification domain, and at least one transcriptional regulatory domain; wherein the TALE domain can be specifically combined with a target nucleotide sequence on an HBV (Hepatitis B Virus) gene and / or a regulatory element of the HBV gene.

The application discloses TaLBD30 protein and an application of a coding gene thereof in regulating a wheat plant type, and belongs to the technical field of biotechnology, and particularly relates to the application of the TaLBD30 protein and the coding gene thereof in regulating the wheat plant type. The protein is any one of the following: A1) a protein with an amino acid sequence as shown in SEQ ID No:1; A2) a protein obtained by substitution, deletion and / or addition of amino acid residues on the protein of A1), the protein being identical to the protein shown in A1) by more than 80% and having the same function; and A3) a fusion protein obtained by connecting a protein tag to the N terminal or / and C terminal of A1) or A2). The TaLBD30 is a transcription factor with transcription inhibition activity, and when overexpressed TaLBD30 , the wheat plant height and ear length are significantly reduced compared with a wild type. TaLBD30 ​

The present invention provides a chromatin-derived genes transcriptional signature suitable to classify two subgroups of prostate cancer patients with different BCR outcome. Gene expression analysis revealed a protective, antitumoral activity of the HDD subtype associated with changes in chromatin compartments and transcriptional repression. The transcriptional signature of the invention confirmed its prognostic relevance across multiple cohorts covering more than 900 prostate cancer patients in total thus providing an innovative strategy for the stratification of primary prostate cancers.

This invention discloses a MYB transcriptional repressor, AsMYB054, related to the synthesis of 2-(2-phenylethyl) chromones in Aquilaria sinensis and its applications. Targeting the weak links in the synthesis and regulation of 2-(2-phenylethyl) chromone compounds, this invention clones for the first time the AsMYB054 gene, a transcriptional repressor related to the regulation of 2-(2-phenylethyl) chromone synthesis in Aquilaria sinensis. AsMYB054 is located in the cell nucleus and possesses transcriptional repressive activity, capable of binding to and inhibiting the activity of the promoters of enzyme genes AsPKS02 and AsPKS09, which are related to the biosynthesis of 2-(2-phenylethyl) chromone compounds. Inhibiting the expression of AsMYB054 using gene editing or RNA interference techniques can promote the accumulation of 2-(2-phenylethyl) chromone compounds in Aquilaria sinensis, showing broad application prospects and significant economic value.

This invention discloses the application of the NbMYB159 gene in the positive regulation of the MVA metabolic pathway in Nicotiana benthamiana, belonging to the field of genetic engineering technology. The technical solution includes the application of the NbMYB159 gene in the positive regulation of the MVA metabolic pathway in Nicotiana benthamiana. The nucleotide sequence of the gene is shown in SEQ ID NO: 1. The NbMYB159 gene can enhance the metabolic flux of the MVA pathway by activating the expression of key structural genes in the Nicotiana benthamiana MVA pathway. This invention discovers that NbMYB159 can specifically bind to the promoter regions of NbHMGR and NbHMGS, activating the expression of all genes in the MVA pathway. Transient overexpression of NbMYB159 in Nicotiana benthamiana significantly increases the content of endogenous FPP in Nicotiana benthamiana. Stable overexpression lines significantly increase the content of endogenous FPP in Nicotiana benthamiana without affecting the biomass of Nicotiana benthamiana, while transcriptional repression overexpression lines significantly reduce the content of FPP. This discovery is of great significance for the engineering modification of the Nicotiana benthamiana chassis and can effectively solve the problem of low production efficiency of sesquiterpenes and triterpenes in Nicotiana benthamiana.

This invention relates to a method based on argB A method for constructing a high-arginine-producing genetically engineered strain using mutants, and the application of this genetically engineered strain in the microbial fermentation production of arginine. The genetically engineered strain was obtained by performing the following gene editing on its genome, starting with Corynebacterium glutamicum ATCC 13032; this invention first involves knocking out the gene encoding the arginine biosynthesis repressor protein. argR and last Relieve transcriptional repression; knock out the gene encoding glutamate kinase. proB Blocking the competitive pathway for the synthesis of the byproduct L-proline; knocking out global nitrogen metabolism regulators. amtR To relieve nitrogen metabolism restriction and enhance nitrogen source supply; to knock out the gene encoding the mechanosensitive channel protein. yggB By altering cell membrane permeability and reducing the leakage of byproducts (such as glutamate), it indirectly promotes arginine accumulation; based on the knockout of the original proB, ldh Replace with Ptac- argB *(T94S, I158V, R273K) strains were constructed to reduce lactic acid byproducts while resisting feedback inhibition; finally, the L-arginine exporter gene was overexpressed via plasmid. lysE By combining the above modification strategies, a genetically engineered strain ARG6-Ptac-, which produces high levels of arginine, was constructed. argB * / pXMJ19- lysE This engineered strain exhibits excellent L-arginine production capacity in both shake flask and fermenter scales (10.3 g / L in shake flask and 105.2 g / L in fed-batch fermentation), and its genetic traits are stable, making it suitable for industrial production.

Provided herein are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, for the transcriptional repression of Hepatitis B viral (HBV) genes to promote a cellular phenotype that leads to the reduction of HBV infection. In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof in a Hepatitis B viral DNA sequence in cell. In some aspects, the provided systems relate to the transcriptional repression of one or more Hepatitis B viral gene and / or regulatory element thereof. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in repressing Hepatitis B viral replication and expression in connection with Hepatitis B infections.

This invention discloses a rutin-containing composition and its applications, belonging to the field of drug development technology. Through molecular docking simulations, animal experiments, and cell experiments, this invention demonstrates that rutin exerts its detoxification effect through a dual mechanism: firstly, it antagonizes the inhibitory effect of α-amatoxins on RNA polymerase II, improving transcriptional repression induced by poisoning; secondly, it alleviates oxidative stress caused by α-amatoxins, reducing MDA content and increasing SOD activity. Rutin significantly improves the survival rate of mice poisoned by α-amatoxins, improves hepatocellular pathological damage, and reduces liver function indicators AST and ALT levels. The optimal dosage is 175 mg / kg, indicating that rutin can be considered a potential therapeutic drug for α-amatoxins poisoning. This invention provides a new treatment option for α-amatoxins poisoning. Rutin is a marketed drug with guaranteed safety and significant advantages for clinical translation.

The invention discloses application of nuclear localization GDOWN1 in preparation of medicines for treating cancers, and relates to the technical field of biological medicines. The engineering modified GDOWN1 protein is localized in a cell nucleus, a brand new anticancer strategy is constructed, the core advantage of the GDOWN1 protein is that the limitation of the existing therapy is broken through, and synergistic anticancer is realized through a double-locking mechanism: on one hand, a p53-p21 pathway is activated to inhibit the activity of cyclin kinase, and on the other hand, the GDOWN1 protein is activated; on the other hand, the transcription process is regulated and controlled to promote dephosphorylation of RB family proteins and activate the transcription inhibition activity of the RB family proteins, and a powerful synergistic effect of cell cycle arrest is formed. The effect is not influenced by the state of the TP53 gene, and a strong proliferation inhibition effect is shown in wild type and mutant type cell strains of chronic myelogenous leukemia, breast cancer and colorectal cancer. In addition, the nuclear localization GDOWN1 has an effective broad-spectrum anti-tumor potential in both p53 wild type and mutant type cancers.

Disclosed herein are improved methods and compositions for diagnosing, preventing and / or treating Huntington's Disease. Among other things, provided herein is a gene therapy construct encoding a non-naturally occurring codon-optimized transcription factor (ZFP-TF) comprising a zinc-finger protein (ZFP) sequence and a sequence encoding a transcriptional repression domain, wherein the ZFP-TF expression is driven by a phosphoglycerate kinase 1 (PGK), ubiquitin C (UBC), an EFS, or an EF1alpha promoter.

For a specific peptide sequence through which AP2α protein binds to a BARX1 promoter region, a small-molecule peptide is researched, developed and utilized by simulating a binding site sequence, so that a binding site for AP2α on a BARX1 promoter can be specifically blocked, the binding of an AP2α complex to the BARX1 promoter can be blocked, an inhibitory effect of AP2α on BARX1 transcription can be alleviated, and BARX1 transcription can be promoted, thereby finally realizing the effects of promoting odontogenic differentiation of odontogenic mesenchymal stem cells and dentin regeneration mediated by odontogenic mesenchymal stem cells within the jawbone, thus improving the success rate of biological tooth root regeneration.

This invention discloses 4-aminopyrimidine LRH-1 receptor antagonists and their applications, belonging to the field of pharmaceutical technology. This invention provides the application of 4-aminopyrimidine compounds and their derivatives, with the general structural formula shown in Formula (I), in the preparation of antitumor drugs. These compounds, as LRH-1 antagonists, exhibit significant downstream transcriptional repression activity against LRH-1 and have a high affinity for LRH-1 LBD protein, effectively inhibiting the proliferation of growth-dependent LRH-1 tumors such as breast cancer, colon cancer, pancreatic cancer, and prostate cancer cell lines. Therefore, these compounds can be applied to the treatment of diseases related to abnormal LRH-1 expression, including but not limited to the treatment of breast cancer, colon cancer, pancreatic cancer, and prostate cancer.

Provided are fusion proteins and DNA-targeting systems for targeted transcriptional repression comprising an effector domain comprising engineered DNA methyltransferase 3 proteins or portions thereof, such as DNA methyltransferase 3L proteins or portions thereof. In some aspects, the compositions and methods provided herein facilitate targeted transcriptional repression by targeting the effector domain to a target site, such as a target site for a target gene. Also provided are methods and uses related to the provided fusion proteins, for example in connection with therapeutic applications.