146 results about "Repressor" patented technology

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

The present disclosure relates to compositions and methods for reducing expression of MYC gene in a cell. In some embodiments, an expression repressor comprises a targeting moiety that binds a MYC promoter, anchor sequence, or super-enhancer. In some embodiments, the expression repressor comprises an effector moiety that represses transcription or methylates DNA. Systems comprising two expression repressors are also disclosed. The compositions can be used, for example, to treat cancers such as HCC.

The present disclosure provides Crispr / cas9-based repressors for silencing gene targets in vivo and methods of use.

A protein capable of inhibiting type I fimbriae of Escherichia coli (E. coli) is identified, where the protein is named as Type I fimbrial repressor (TIFR) protein, and is encoded by a TIfr gene with an ID of GW576_23830. A method is further provided for inhibiting the growth of type I fimbriae of an E. coli strain, in which the TIfr gene is transformed into the strain.

Provided herein are compositions, methods, and systems for DNA modification. In particular, provided herein are compositions, and systems comprising TnpB-like nuclease-dead repressors (dTnpB / TldRs), dCas12f or dCas12f-like proteins, and / or a TnpB-transposase fusion proteins and methods using thereof.

The invention discloses a method for constructing an engineered bacterium of Clostridium aeruginosa, comprising the following steps: preparing a desired gene in a biosynthetic pathway of a target product, namely a pathway gene, to form a pathway gene cluster; embedding the pathway gene cluster into a transposase recognition site of a mariner transposon to form a pathway gene expression cassette; selecting a constitutive strong promoter commonly used in Clostridium jundal for driving transposase expression, loading the pathway gene expression cassette into a multiple cloning site of a plasmid, and inserting an inducible repressor element upstream of the replicon to obtain a transposition plasmid; transforming the transposition plasmid into Clostridium aeruginosa to obtain an engineered bacterium of Clostridium aeruginosa. The yield of 3-hydroxybutyric acid expressed by the engineered bacterium constructed by the above method is as high as 3g / L.

A genetically modified yeast cell, wherein the yeast cell comprises a genetic modification comprising overexpression of yeast gene encoding porphobilinogen deaminase (HEM3), the HEM3 gene having at least 80% identity with SEQ ID No. 7. The genome of the modified yeast cell further comprises one or more genetic modifications in one or more genes selected from: genes coding for heme-dependent repressor of hypoxic genes (ROX1), genes coding for heme oxygenase (HMX1), genes coding for a receptor for vacuolar proteases (VPS10), and genes coding for vacuolar proteinase (PEP4), the one or more genetic modifications being such that expression of a polypeptide from such a gene is reduced or disrupted or the polypeptide expressed is non-functional.

The invention belongs to the technical field of biological medicines, and discloses an engineered bacterium for in-situ expression of a microtubule inhibition protein in a tumor and application of the engineered bacterium. The engineering bacteria are formed by constructing microtubule inhibition protein genes to an expression vector and finally transferring the expression vector into bacteria. The engineering bacterium can be colonized in a tumor microenvironment in a targeted manner, expresses microtubule inhibition protein, effectively inhibits tumor cells and remarkably inhibits solid tumor growth, and is excellent in safety.

The present application relates to: a novel gluconate repressor variant, a polynucleotide comprising the variant of the present application, a microorganism of the genus Corynebacterium comprising the variant of the present application or the polynucleotide, and a method for producing L-arginine using the microorganism of the present application.

To provide, generally, methods and compositions for transferring a genetic circuit from one prokaryotic cell ("donor cell") to another prokaryotic cell ("recipient cell" or "target cell" used interchangeably herein).SOLUTION: The present disclosure relates to: prokaryotic donor cells comprising (i) a genetic circuit of interest and (ii) one or more expressed transcriptional repressor proteins; and the use of the donor cells in efficient transfer of the genetic circuit into a prokaryotic recipient cell. The genetic circuit includes nucleic acid sequences encoding an RNA molecule or protein of interest.SELECTED DRAWING: None

The inventions provide mammalian cell lines integrated with recombinant adeno-associated virus (rAAV) plasmids, cell genomes and methods of making the cell genomes for production of rAAV. The inventions also provide regulatory fusion proteins (RFPs) (which can act as activators or repressors) and repressor proteins (which act as repressors), such as antibiotic repressors, and arranged operators to control transcription of at least one polynucleotide of interest, such as AAV Rep genes and / or non-AAV helper genes.

The present disclosure is directed to novel therapeutic approaches for the prevention, treatment and / or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of an organ. Specifically disclosed are agents for use in increasing homodimer-formation of ARNT in an organ in the prevention, treatment and / or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of said organ, as further defined in the claims. In embodiments, said agent may be (i) an inhibitor of protein phosphatase 2A (PP2A) activity, (ii) an inhibitor of the transcriptional repressor complex FKBP12 / YY1, or (iii) an expression construct, which is capable of over-expressing ARNT in said organ, as well as combinations of (i), (ii), and / or (iii).

Disclosed herein are polypeptide fragments and polynucleotides based on mutant capicua transcriptional repressor (CIC), catenin beta 1 (CTNNB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog B (ERBB2), kirsten rat sarcoma (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), splicing factor 3b subunit 1 (SF3B1), SRY-box transcription factor 17 (SOX17), tumor protein 53 (TP53), and cytomegalovirus (CMV) sequences, vectors, host cells, viruses, methods for generating CD8+ T-cells, and methods of treatment. Also disclosed herein are T-cell receptors (TCRs), polynucleotides, vectors and cells comprising the TCRs, and methods of treatment.

A complex, comprising a first fusion and a second fusion, wherein one of the first fusion and the second fusion comprises a DNA methylation domain and at least one recruitment domain A, and the other fusion comprises a transcriptional repressor domain and at least one recruitment domain A′; and the recruitment domain A and the recruitment domain A′ interact with each other, so that one of the first fusion and the second fusion or a part thereof is recruited to the vicinity of the other fusion. Also provided are use of the complex in the preparation of a product for inhibiting target gene expression and the preparation of a drug.

This article provides gene repressor systems that can be used to repress genes, the gene repressor systems comprising repressor fusion proteins, such as repressor fusion proteins containing DNA-binding proteins, in some cases catalytically dead CRISPR proteins, and guide nucleic acids (gRNA). Methods for using such systems to repress gene transcription are also provided.

Recombinant phages that infect and kill bacterial hosts in response to user-defined inputs are provided. The components that encode the user-defined inputs can be combined, such that multiple inputs are maintained on a single recombinant phage, enabling precise control over the targeting strategy. The phages can be engineered to kill a specific bacterial species or multiple species simultaneously. Recombinant phages can also be engineered to harbor fluorescent and bioluminescent reporter genes that enable them to be used for tracking, detection, and in biosensing applications. Recombinant phages can also be used to lyse bacterial cells that produce recombinant proteins, as a rapid method to enable extraction and high-level purification of potentially valuable and / or industrially important proteins. Systems are provided that can be used to control the activity of a protein of interest, by taking advantage of an interaction between Qtip and a phage repressor protein.

This invention discloses a genetically engineered bacterium for synthesizing carotenoids, its construction method, and its applications, belonging to the field of genetic engineering technology. The genetically engineered bacterium uses a carotenoid-producing yeast strain as the starting material. The gene ROX1, encoding a heme-dependent hypoxia gene repressor, is knocked out, while the expression of genes STB5 (encoding a transcription factor involved in NADPH regeneration), DID2 (encoding a class E protein in the vacuole protein sorting pathway), and VOA1 (encoding an endoplasmic reticulum protein playing a role in the assembly of the V0 region of V-ATPase) is upregulated. This invention promotes carotenoid synthesis and significantly increases carotenoid yield through combined regulation of gene expression outside the carotenoid synthesis pathway, demonstrating promising application prospects.

Provided herein are compositions and methods for treating an autoimmune disease or disorder in a subject. In some cases, the compositions and methods use chemical inducers of proximity (CIPs). In some cases, the CIPs include a first moiety having specific binding for a BTB domain-containing protein or a transcriptional repressor expressed in B cell subpopulations and a second moiety having specific binding for a modulator of gene regulation. In some cases, the BTB domain-containing protein comprises BCL6. In some cases, the transcriptional repressor expressed in B cell subpopulations is PRDM1 or IRF4. In some cases the modulator of gene regulation comprises BRD4, CDK9, and / or p300.

The disclosure features compositions or systems and uses thereof, comprising a first polynucleotide encoding a target molecule, optionally a second polynucleotide encoding an effector, repressor, or endonuclease molecule; optionally a recognition or cleavage site in the first or second polynucleotide, and optionally a repressor / effector binding site in the first polynucleotide. The disclosure also features compositions or systems and uses thereof, comprising a messenger RNA (mRNA) comprising (i) an open reading frame encoding a polypeptide, and (ii) at least six miR142 target sites.

Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guid

The invention discloses a GlcNAc6P induction component and a method for promoting synthesis of acetylglucosamine. The existing GlcNAc6P sensing element has the problems of serious leakage and small response range, which results in that in the process of regulating and controlling the expression of phosphatase by using the GlcNAc6P sensing element, the phosphatase also has higher expression intensity when intracellular GlcNAc6P is not accumulated, and the supply of precursor substances is influenced. Besides, along with rapid increase of the intracellular GlcNAc6P concentration, the upper limit of the expression quantity of phosphatase is low, the intracellular dephosphorylation requirement cannot be met, and further increase of the GlcNAc yield is limited. Therefore, an existing GlcNAc6P sensing element is optimized, a nagC binding sequence is subjected to directed evolution, expression intensity of repressor protein nagC is optimized, the leakage expression level of the sensor is reduced, and the response range of the sensor is expanded, so that the expression intensity of phosphatase is more effectively and rigorously regulated and controlled to adapt to the change of the concentration of GlcNAc6P in cells in different fermentation periods; and a foundation is laid for producing acetylglucosamine by further transforming recombinant bacteria through metabolic engineering.

To provide improved gene therapy vectors comprising a polynucleotide sequence encoding a TCIRG1 polypeptide or a functional variant thereof, methods of use thereof, pharmaceutical compositions, and more, and in particular, to provide lentiviral vectors for treatment of infantile malignant osteopetrosis (IMO).SOLUTION: Provided is a transfer plasmid, comprising an expression cassette comprising a coding polynucleotide encoding a T cell immune regulator 1 (TCIRG1) polypeptide and a promoter, wherein the polynucleotide is operatively linked to the promoter, and wherein the transfer plasmid comprises an RNA-OUT repressor and a CMV IE promoter, and also comprises a polynucleotide sharing at least 95% identity to a specific sequence.SELECTED DRAWING: Figure 1

The application relates to methods for identifying putative regulatory elements that regulates a gene, comprising: obtaining a measure of intrinsic activity of a plurality of genomic elements; obtaining a measure of proximity between each of the genomic elements and the gene; scoring a predicted impact of each of the genomic elements on the gene as a function of the measure of intrinsic activity and the measure of proximity, wherein a plurality of predicted impacts scored are ranked to identify at least one genomic element as a putative regulatory element that regulates the gene; and optionally, training, optimizing, and / or validating the scoring of predicted impact using experimental or computational data describing functional interactions between the genomic elements and the gene. The application also relates to methods for identification of transcriptional enhancers and repressors regulating a gene associated with an agricultural trait of interest in plants or a disease phenotype in mammalians.

The present disclosure relates to compositions and methods for reducing the expression of the MYC gene in cells. In some embodiments, the expression repressor comprises a targeting moiety that binds to the MYC promoter, an anchor sequence, or a super enhancer. In some embodiments, the expression repressor comprises an effector moiety that suppresses transcription or methylates DNA. A system comprising two expression repressors is also disclosed. The compositions can be used, for example, for the treatment of cancers such as HCC.

The invention belongs to the technical field of gene engineering, and particularly relates to application of CmIAA27 in regulation and control of lateral branch development of chrysanthemum. According to the invention, phenotypic analysis is carried out on a CmCMT2-RNAi transgenic 'Shenma' plant obtained at an earlier stage, and lateral branches of the CmCMT2-RNAi transgenic 'Shenma' are increased in a vegetative growth period. RNA-seq is carried out on the gene CmIAA27, it is found that the expression quantity of the auxin inhibitory signal key gene CmIAA27 is remarkably increased, McrBC and BSP experiments show that the CHH type methylation level on a CmIAA27 promoter in a transgenic line is remarkably lower than that of WT, and the expression of the plant lateral branch development key inhibitory gene CmBRC1 in the transgenic line is remarkably reduced. Y1H, LUC and EMSA experiments show that the CmCMT2 can be directly combined with a CmIAA27 promoter and regulate and control the CHH type methylation level in the region so as to influence the expression of the CmIAA27. Through transcription analysis of CmCMT2-RNAi transgenic Shenma and WT, a key factor CmIAA27 for downstream regulation and control of chrysanthemum lateral branch development is obtained, functional verification is carried out, and excellent gene reserve and a new strategy are provided for regulation and control of chrysanthemum lateral branches.

Provided are plasmids comprising transcriptional control elements, including transcription factor binding motifs, telomeric repeat motifs, transcription factor repressor binding motifs and promoters for tunable protein expression in target cells; wherein the plasmid for controlled transcription in a target cell type comprises a transcription factor binding motif for NFIA and the cell expresses NFIA. In one embodiment, the cell type is lung cells and the transcription factor is Nuclear Factor IA (NFIA).

The present invention discloses the construction and application of a screening system for lactose or its analog biosensors in Bacillus subtilis. The present invention designs a "dual-screening" biosensor repressor screening gene circuit based on the lactose operon and applicable to Bacillus subtilis: the DNA binding activity of the repressor is screened through a negative screening lethal circuit; the allosteric activation activity is screened through a positive screening fluorescence signal; and finally, a biosensor with the recognition activity of the target lactose analog is obtained. Using this screening platform, novel biosensors responsive to substances such as lactose, 2'-fucosyllactose, and 3-fucosyllactose can be obtained. Moreover, it has been verified that the biosensors constructed according to the screening results of the present invention have high detection sensitivity and specificity.

Novel gene repressor systems are provided that are useful in animal cells that include engineered repressors with altered ligand-binding domains (LBDs) and DNA-binding domains (DBDs), as well as mutated operator sequences. In one aspect, the systems enable independent, drug-inducible control of multiple genes within a single animal or animal cell line. In one aspect, the disclosure provides both tetracycline-responsive repressors and sulfonylurea (SU)-responsive repressors — e.g., variants that respond specifically to ethametsulfuron-methyl (Es) or chlorsulfuron (Cs). Mutations are introduced to either the LBD (to alter ligand specificity), DBD (to alter operator binding), or the operator sequence itself, resulting in orthogonal systems.

The invention relates to the technical field of gene engineering, in particular to a bidirectional promoter Para *, an araa * expression system, application and an engineering strain. The araa * expression system comprises the bidirectional promoter Para *, a repressor protein araR gene module is arranged on one side of the bidirectional promoter Para *, and a fluorescent protein gene module is arranged on the other side of the bidirectional promoter Para *. Wherein the repressor protein araR gene module comprises a repressor protein araR gene and a first RBS sequence corresponding to the repressor protein araR gene; and the fluorescent protein gene module comprises a fluorescent protein gene and a second RBS sequence corresponding to the fluorescent protein gene. By characterizing and designing an exogenous inducible promoter, an ara * expression system capable of realizing inducible expression in xanthomonas campestris is obtained, and a basic element is provided for construction of a xanthomonas campestris genetic engineering strain.