135 results about "Regulatory sequence" patented technology

To provide a medicine for treating a disease in a mammal.SOLUTION: Provided is a medicine for treating a disease in a mammal, comprising an expression cassette that is a first expression cassette comprising a chimeric gene operably linked to a first expression control element, the chimeric gene comprising a first portion comprising a minigene having an alternatively spliced exon and a second portion encoding a first RNA encoding a protein, the first portion being 5' to the second portion, the second portion lacking an initiation codon or start codon, the alternatively spliced exon comprising a translation initiation regulatory sequence, expression of the protein being controlled by inclusion of the alternatively spliced exon, and the medicine being used in combination with a small molecule splicing modifier that modulates splicing of the alternatively spliced exon.SELECTED DRAWING: Figure 1

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5' inverted terminal repeat (ITR), an expression cassette comprising engineered nucleic acid sequence encoding human Tafazzin and operably linked thereto regulatory sequences, and an AAV 3' ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treatment of Barth Syndrome or a disease associated with a mutation in a Tafazzin (TAZ) gene.

The present disclosure provides methods and systems for identifying transcriptional regulatory modules (e.g., in non-coding portions of the genome), predicting gene regulation and expression, e.g., effects of non-coding mutations or chromosome rearrangements on the regulation and expression of the target genes, and designing and using modified regulatory sequences.

The invention discloses a 5 'UTR library, a recombinant expression vector and a genetically engineered bacterium for improving the yield of folamin in pathogenic bacterium Badei and application of the 5' UTR library and the genetically engineered bacterium, and belongs to the technical field of microbial genetic engineering. The method comprises the following steps: designing an SD region based on a 16S rRNA (ribosomal Ribonucleic Acid) 3'end complementary sequence of a Buddei pathogenic bacterium XBD101 serving as an original strain, regulating and controlling the number of bases between the SD sequence and an initiation codon AUG and optimizing an UTR secondary structure to construct a library containing 14 UTR sequences, and replacing three sequences N4A, N7A and N18A with the strongest translation ability in the library to the UTR region of a folamin synthesis key gene fclC, so as to obtain the folamin peptide. And finally, the capacity upgrading of the folamin chassis strain is realized, and an important support is provided for the industrial production of agricultural antibiotics.

To provide recombinant adeno-associated viral vectors for treating Bietti Crystalline Dystrophy.SOLUTION: Provided are a recombinant adeno-associated vector comprising a codon-optimized sequence encoding CYP4 V2 linked to predetermine gene expression regulatory sequences, and its use in treating Bietti Crystalline Dystrophy (BCD).SELECTED DRAWING: None

The invention relates to an endoplasmic reticulum targeting polypeptide nano-drug with glutathione responding to morphology transformation, a preparation method and a related performance characterization method. The endoplasmic reticulum targeting polypeptide nano-drug with glutathione responding to morphology transformation comprises a targeting unit, an assembling unit and a functional unit, wherein the targeting unit comprises one or more of targeting peptide sequences RVMLIGK, RVMLIEK, KDEL and sulfonyl groups with an endoplasmic reticulum targeting function; the functional unit comprises a glutathione response group disulfide bond, and the assembly primitive sequence and the assembly regulation sequence are covalently connected through the disulfide bond. The assembly structure of the polypeptide nano-drug has sensitive glutathione responsiveness, so that the polypeptide nano-drug can generate assembly morphology transformation in glutathione overexpressed tumor cells, and the polypeptide nano-drug is simple and convenient to synthesize and prepare and has wide application prospects in the aspects of drug delivery, tumor treatment and the like.

The invention relates to the technical field of molecular breeding, and discloses an auxin amide hydrolase RhILL1 gene and application of the auxin amide hydrolase RhILL1 gene in regulation and control of China rose flower color, and the nucleotide sequence of the auxin amide hydrolase RhILL1 gene is shown as SEQ ID NO.1. By silence or overexpression of the RhILL1 gene, synthesis of anthocyanin is effectively regulated and controlled, and accurate control of petal color is realized. Researches find that silencing of the RhILL1 gene leads to color fading of petals and reduction of anthocyanin content; and overexpression of the RhILL1 gene prolongs the color holding time of the petals. In addition, the invention also provides a kit containing the RhILL1 gene regulatory sequence, a recombinant plasmid and a corresponding gene editing and transgenic breeding method. The achievements provide a new molecular tool for Chinese rose breeding and flower color improvement, and have important ornamental value and economic significance.

A dual vector system for treating ornithine transcarbamylase deficiency is provided. The system includes ((a) a gene editing AAV comprising a first AAV rh79 capsid and a first vector genome comprising a 5′ ITR, a sequence encoding a meganuclease that targets PCSK9 under control of regulatory sequences that direct expression of the meganuclease in a target cell comprising a PCSK9 gene, and a 3′ ITR; and(b) a donor AAV vector comprising a second AAV capsid and a second AAV rh79 vector genome comprising: a 5′ITR, a 5′ homology directed recombination (HDR) arm, a transgene encoding ornithine transcarbamylase (OTC) and regulatory sequences that direct expression of the transgene in the target cell, a 3′ HDR arm, and a 3′ ITR.

A method for generating a gene regulatory sequence with a desired endophenotype profile includes obtaining a plurality of gene regulatory sequences and inputting the plurality of gene regulatory sequences into a machine-learning model trained to obtain a plurality of effect predictions corresponding to a plurality of endophenotypes. The method further includes selecting one or more desired endophenotypes based on the plurality of endophenotypes and selecting a gene regulatory sequence in accordance with the one or more desired endophenotypes.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, optionally comprising stabilizing amino acid changes, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

The invention provides an artificial plant bidirectional constitutive strong promoter, and particularly relates to a high-activity short transcription enhancer fragment which is formed by connecting three plant endogenous fragments and a plant virus in series and serves as a transcription activation basic element. A minimum core promoter element Mini 35S from a cauliflower mosaic virus and a minimum core promoter element CsVMV mini-pro functional module from a cassava vein mosaic virus are respectively integrated at two ends, so that the plant constitutive strong promoter with bidirectional starting capability is constructed. According to the invention, a synthetic quadruple STE transcription enhancer, a Mini 35S promoter and a CsVMV mini-pro promoter are functionally coupled to form an expression regulation tool with broad-spectrum adaptability to plant species, and two operably connected target gene expression cassettes can be simultaneously driven by a short regulation sequence to realize synergistic efficient expression in plant cells.

The invention discloses a method for efficiently preparing fixed-point biotinylation recombinant protein in escherichia coli, and belongs to the technical field of biology. According to the invention, a weakened expression regulatory sequence regulates and encodes a biotin ligase (BirA) gene expression cassette and a target protein gene expression cassette encoding a sequence carrying a biotin receptor peptide tag (AVI-Tag) to be jointly constructed on an escherichia coli expression vector, so that efficient fixed-point biotinylation of a target protein in an escherichia coli body is realized. The method has the advantages of high biotinylation efficiency, high specificity, simplicity and convenience in operation and the like, can be widely applied to the fields of separation and purification of proteins, protein interaction research and the like, and has important practical application value.

The present disclosure provides a recombinant adeno-associated vector comprising a codon-optimized sequence encoding CYP4V2 linked to selected gene expression regulatory sequences and its use in treating Bietti Crystalline Dystrophy (BCD).

The invention provides a nucleic acid construct which comprises an immune response regulatory sequence and a coding sequence of a reporter gene driven by a promoter sequence, and the immune response regulatory sequence comprises a transcription factor binding regulatory element RE which is co-stimulated and regulated by transcription factors AP-1 and CD28. The invention also provides an in-vitro immune effector function reporter gene cell model containing the nucleic acid construct, and the cell model can realize effector function activity determination performance of sensitive and potent signals so as to evaluate ADCC and ADCP killing action mechanisms and titers mediated by antibody-dependent disease cells designed by an Fc structural domain of a therapeutic antibody product. In addition, the immunosuppression and regulation efficacy of a targeted CTLA-4 or Abatacept mediated treatment method on a CD28 co-activation pathway can be evaluated.

Methods and compositions for treating a corneal wound and / or increasing a population of limbal epithelial stem cells (LESCs) and / or early transit amplifying cells (eTAs) in the limbal epithelium of a subject in need thereof. The methods can include administering a therapeutic agent to the subject that: i) results in an increase in concentration of IFITM1 (Interferon Induced transmembrane Protein 1) in the limbal epithelium of the subject; and / or ii) results in a decrease in concentration of OVOL1 (Ovo Like Zinc Finger 1) in the limbal epithelium of the subject. Also provided are adeno-associated viruses (AAVs). The AAVs comprise a heterologous nucleic acid sequence encoding IFITM1 or a variant thereof, operably linked to a regulatory sequence.

Systems and methods for producing multiple unique edits in T1 seeds of a plant are provided. In one example, the method includes transforming at least one expression cassette into a plant cell or plant tissue. The at least one expression cassette may include a nucleic acid encoding a DNA modification enzyme; optionally, a nucleic acid encoding at least one guide RNA (gRNA); and a floral mosaic (FMOS) regulatory sequence, wherein the FMOS regulatory sequence (i) mediates the expression of the DNA modification enzyme in at least one of a flower primordium cell and a flower reproductive organ, and (ii) mediates multiple edits in at least one of the flower primordium and the flower reproductive organ. The method may also include regenerating the plant cell or plant tissue into a TO plant having multiple T1 seeds, wherein the T1 seeds contain multiple unique edits.

The invention also provides a polynucleotide regulatory sequence which can be used for increasing the protein expression level of the protein expression system, a protein expression vector or a protein expression system containing the regulatory sequence, and application of the polynucleotide regulatory sequence and the protein expression vector or the protein expression system. The use of regulatory sequences can increase the expression level of heterologous proteins. When used in a viral expression system, the regulatory sequence can also increase the titer of viral particles.

The invention discloses a temperature-controlled cleavage plasmid based on nut site deletion of a pL promoter as well as a construction method and application of the temperature-controlled cleavage plasmid. According to the invention, on the premise of keeping the lambda cI857-pL / pR temperature control regulation mode unchanged, the stability of the system under medium-high temperature culture conditions is improved; meanwhile, compared with other systems for realizing thermal stability through promoter mutation, the system disclosed by the invention effectively relieves the problem that the cracking efficiency is obviously reduced after temperature rise induction by carrying out directional deletion transformation on a downstream regulation sequence of the promoter, so that the cracking process is more sufficient and reliable, and particularly, host bacteria can still be efficiently cracked under the induction condition of 42 DEG C; the bacteria dissolving efficiency can reach 99.99% or above, and the problem that the thermal stability and the cracking efficiency are difficult to consider in the bacterial ghost preparation process is solved.

Systems and methods for generating a plurality of unique edits in a T1 seed of a plant are provided. In one example, a method includes transforming at least one expression cassette into a plant cell or plant tissue. The at least one expression cassette may comprise a nucleic acid encoding a DNA modifying enzyme; optionally, a nucleic acid encoding at least one guide RNA (gRNA); and a floral mosaic (FMOS) regulatory sequence wherein the FMOS regulatory sequence (i) mediates expression of the DNA modifying enzyme in at least one of a floral primordium cell and a floral reproductive organ, and (ii) mediates a plurality of edits in at least one of the floral primordium and the floral reproductive organ. The method may also include regenerating the plant cell or plant tissue into a TO plant having a plurality of T1 seeds, wherein the T1 seeds contain a plurality of unique edits.

The purpose of the present invention is to provide a transformant having excellent 2,3-butanediol production capability. Provided is a transformant of a hydrogen-oxidizing bacterium that grows in the co-presence of oxygen, the transformant being used for the production of 2,3-butanediol. In the transformant, (a) a nucleic acid encoding an enzyme for synthesizing acetolactate from pyruvic acid, (b) a nucleic acid encoding an enzyme for converting acetolactate into acetoin, (c) a nucleic acid encoding an enzyme for converting acetoin into 2,3-butanediol, and (d) a regulatory sequence operably linked to the nucleic acids (a) to (c) are introduced, wherein the nucleic acid (b) is located upstream of the nucleic acid (a) and the nucleic acid (c).

Plant T-DNA expression vectors encoding a post-translational modification (PTM) enzyme wherein the nucleic acid encoding the PTM enzyme has neither a promoter nor a 5′ untranslated region (UTR) are provided. Also provided are methods of optimizing expression and glycosylation of recombinant protein produced in plants by utilizing the plant T-DNA expression vectors.

The invention discloses an inflammation regulation sequence of dairy cow mastitis and application thereof, and belongs to the technical field of biology, the inflammation regulation sequence is a regulation sequence responding to a gram-negative bacterium inflammation signal, the regulation sequence is a promoter sequence of a CXCL2 gene and is shown as SEQ ID NO: 1, and the regulation sequence is a promoter sequence of a CXCL2 gene and is shown as SEQ ID NO: 2. A regulatory sequence responding to a gram-positive bacterium inflammation signal, which is a promoter partial sequence of the NLRP3 gene and is as shown in SEQ ID NO: 2; the regulatory sequence responding to a gram-positive bacterium inflammation signal is a promoter reverse complementary sequence of the TLR2 gene and is shown as SEQ ID NO: 3; the endogenous inflammation regulation sequence provided by the invention is composed of genome elements of the dairy cow, and no exogenous coding gene is introduced, so that potential risks caused by exogenous proteins are avoided.

The present invention provides genetic constructs and methods for enhanced production of milk proteins in transgenic plants. The invention comprises novel nucleic acid constructs wherein regulatory sequences derived from plant genes are inserted into bovine casein coding sequences, resulting in increased protein accumulation when expressed in plant cells. In particular embodiments, the insertion of these regulatory sequences into casein coding sequences leads to enhanced protein accumulation in transgenic soybean plants compared to constructs lacking the regulatory sequences.

The present invention relates to functional nucleic acid molecules for use in upregulating OPA1 expression. The functional nucleic acid molecules typically comprise at least one target binding sequence reverse complementary to an OPA1 mRNA sequence and at least one regulatory sequence which comprises a SINE B2 element or an internal ribosome entry site (IRES) sequence. Also described are therapeutic methods of using the functional nucleic acids.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

Provided herein, among other things, is a cell-based therapeutic for the treatment of a non-malignant disease of the lung. In some embodiments, the therapeutic may comprise a cell comprising a molecular circuit comprising: (i) a binding-triggered transcriptional switch (BTTS) that binds to RAGE (Receptor for Advanced Glycation Endproducts), (ii) a nucleic acid sequence encoding an immunosuppressive protein, a growth factor and / or an anti-fibrotic agent; and (iii) a regulatory sequence operably linked to (ii) that is responsive to the binding-triggered transcriptional switch, wherein binding of the binding-triggered transcriptional switch to RAGE activates expression of the immunosuppressive protein, growth factor and / or the anti-fibrotic agent in the lung. Alternatively or in addition, the therapeutic may be a T cell (Treg) comprising an engineered immune receptor that recognizes RAGE. Also provided is a method for decreasing inflammation in the lung and / or inducing repair of lung tissue.

Systems and methods for generating a plurality of unique edits in a T1 seed of a plant are provided. In one example, a method includes transforming at least one expression cassette into a plant cell or plant tissue. The at least one expression cassette may comprise a nucleic acid encoding a DNA modifying enzyme; optionally, a nucleic acid encoding at least one guide RNA (gRNA); and a floral mosaic (FMOS) regulatory sequence wherein the FMOS regulatory sequence (i) mediates expression of the DNA modifying enzyme in at least one of a floral primordium cell and a floral reproductive organ, and (ii) mediates a plurality of edits in at least one of the floral primordium and the floral reproductive organ. The method may also include regenerating the plant cell or plant tissue into a TO plant having a plurality of T1 seeds, wherein the T1 seeds contain a plurality of unique edits.

Provided are gene therapy vectors designated MEV-GTVs, which are MEVs that contain an ITR-containing plasmid (also referred to as a minigene plasmid) that comprises Inverted Terminal Repeats (ITRs), such as viral ITRs, and nucleic acid encoding a product of interest, and optionally regulatory sequences. The ITRs serve to circularize the minigene plasmid. The plasmids do not contain additional viral components, so that resulting DNA is not encapsulated in a viral capsid or envelop and is not replicated by viral genes. The plasmids can be inserted into bacterial plasmids for propagation.

This invention describes a novel gene regulatory sequence containing the promoter and enhancer sequences of the human cardiac troponin T gene (TNNT2) that selectively induces expression in cardiomyocytes. This novel TNNT2 promoter / enhancer composition can be used to induce adeno-associated virus gene expression, construct cell-type-specific expression vectors, or perform cardiac-specific transgenesis. The use of this novel promoter / enhancer composition is demonstrated by the expression of mAKAP shRNA and a mAKAP-derived anchor-disrupting peptide useful for the treatment of heart failure.

The present disclosure relates to a regulatory sequence that drives gene expression, a construct including an ATM gene operably linked to the regulatory sequence, and an adenovirus vector including the construct.