44 results about "Regulatory sequence" patented technology

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.

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.

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 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.

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.

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.

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.

Provided herein are vectors with engineered regulatory sequences for expression of non-coding RNAs (ncRNAs). Regulatory sequences of expression vectors include a Pol III promoter and a binding site for a Pol II - associated transcription factor. Also provided are compositions comprising provided vectors and methods of using the same, e.g., for expression of ncRNAs, e.g., for gene editing.

A recombinant AAV (rAAV) suitable for use in treating adult onset neurodegeneration caused by granulin (GRN) haploinsufficiency, such as progranulin (PGRN)-related frontotemporal dementia (FTD), is provided. The rAAV comprises (a) an adeno-associated virus 1 capsid, and (b) a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin. Also provided are a method for treating a human patient with PGRN-FTD and other adult onset neurodegeneration caused by granulin (GRN) haploinsufficiencies, comprising delivering to the central nervous system (CNS) a recombinant adeno-associated virus (rAAV) having an adeno-associated virus 1 (AAV1) capsid, said rAAV further comprising a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin.

The present invention relates to minimal polypeptide-encoding RNA molecules, in particular, RNA molecules that lack or comprise shortened regulatory sequences as compared to those found in eukaryotic mRNAs, which are thus more amenable to chemical synthesis. The invention also encompasses compositions comprising distinct populations of said RNA molecules, each encoding a unique polypeptide, and methods for manufacturing and using the RNA molecules or compositions.

A dual component system for treating a genetic disorder is provided. The system includes (a) a gene editing vector comprising an expression cassette comprising a nucleic acid sequence encoding a nuclease and regulatory sequences that direct expression of the nuclease in a target cell comprising a PCSK9 gene; and (b) a donor vector comprising a nucleic acid sequence encoding an exogenous product for expression from the PCSK9 locus, wherein the inserted nucleic acid sequence does not encode PCSK9, wherein the system further comprises sequences that direct the nuclease to specifically targets the native PCSK9 gene locus; and wherein the native PCSK9 in the target cell is optionally ablated or reduced post-dosing with the dual component system.

The present disclosure provides nucleic acid constructs engineered to express therapeutic expression products from regulatory sequences that drive expression in hematopoietic cell populations. For example, the present disclosure includes nucleic acid constructs in which a first regulatory sequence drives expression of a first therapeutic expression product and a second regulatory sequence drives expression of a second therapeutic expression product. Nucleic acid constructs can be delivered to cells or subjects by viral vectors, including adenoviral vectors, e.g., for the treatment of cancer.

To provide methods and compositions for modulating a target genome.SOLUTION: The present disclosure relates to compositions, systems, and methods for targeting, editing, modifying, or engineering a DNA sequence (e.g., inserting a heterologous DNA sequence of interest into a target site of a mammalian genome) at one or more locations within a DNA sequence in a cell, tissue, or subject, e.g., in vivo or in vitro. The DNA sequence of interest may comprise, for example, a coding sequence, a regulatory sequence, a gene expression unit.SELECTED DRAWING: None

This invention relates to the field of plant molecular marker technology, specifically to an EST-SSR molecular marker primer set developed based on the transcriptome sequence of *Prunus campanulata* and its applications. The EST-SSR molecular marker primer set contains 19 pairs of primers, with sequences shown in SEQ ID Nos. 1–38. The EST-SSR molecular marker primers developed based on *Prunus campanulata* transcriptome data exhibit greater accuracy, stability, and effectiveness compared to traditional molecular markers. Furthermore, the EST-SSR markers are mostly distributed in regions related to gene coding regions or regulatory sequences, providing a theoretical basis and important technical means for *Prunus campanulata* germplasm resource identification, genetic diversity analysis, molecular-assisted breeding, and fingerprinting, and have promising application prospects.

The technology described herein is directed to systems and methods for synthetic regulatory sequence design or production. In several aspects described herein are methods of designing and optionally synthesizing shortened or otherwise modified polynucleotide sequences from polynucleotide sequences with transcriptional regulatory functionality. In other aspects described herein are isolated nucleic acid modules and viral vectors, comprising said shortened or otherwise modified polynucleotide as designed or synthesized herein.

The invention discloses a construction method and application of an hMRGPRX3 humanized mouse model and an atopic dermatitis model, and relates to the technical field of disease model construction. The whole gene sequence of the human MRGPRX3 or a vector containing the gene sequence of the hMRGPRX3 is transferred into mouse genome DNA (Deoxyribonucleic Acid) by utilizing a transgenic technology, and a functional human hMRGPRX3 receptor can be simulated and expressed in a mouse model more truly by transferring upstream and downstream regulatory sequences of the hMRGPRX3 gene. The pruritus signal transduction mediated by the receptor in human dorsal root ganglion sensory neurons can be accurately simulated, and signal deviation caused by species difference of a traditional mouse model is overcome.

The present disclosure discloses a new Retron editing system and its application in Corynebacterium glutamicum gene editing, specifically discloses a new Retron editing system and demonstrates its application in Corynebacterium glutamicum gene editing, belonging to the technical field of biotechnology and genetic engineering. The new gene editing system provided by the present disclosure is obtained by modifying the existing Retron editing system, which improves the efficiency and capacity of gene editing. The gene editing system of the present disclosure is applied to the construction of a DNA fragment genomic in situ saturation mutation library, which has high construction efficiency, high mutation site coverage and comprehensive mutation types. This method has broad application prospects in the fields of multi-gene editing regulation, DNA regulatory sequence in situ library construction, protein coding gene in situ library construction, enzyme high-throughput screening and the like.

A recombinant adeno-associated virus (rAAV) useful for treating type II glycogen storage disease (Pompe) disease is provided. The rAAV comprises an AAV capsid which targets cells of at least one of muscle, heart, kidney, and the central nervous system and which has packaged therein a vector genome comprising a nucleic acid sequence encoding a human acid-α-glucosidase hGAA780I protein or fusion protein under the control of regulatory sequences which direct its expression. Also provided are methods of making and using this rAAV.

The application discloses a nucleic acid molecule targeting SARS-CoV-2 virus Spike protein, a recombinant expression vector comprising the same and application. The nucleic acid molecule comprises a promoter and a downstream regulatory sequence, wherein the regulatory sequence comprises an antisense oligonucleotide, a nucleic acid sequence encoding a RING domain of TRIM21 and a nucleic acid sequence encoding a specific binding domain of a target protein. The design simultaneously realizes translation inhibition and ubiquitination degradation of the target protein through a single vector, significantly improves the inhibition efficiency of the target protein and provides a new efficient and simple strategy for protein targeted degradation.

An isolated nucleic acid sequence including at least two copies of a miRNA target site of the miR183 family having a sequence as set forth in SEQ ID NO: 1, SEQ ID NO: 21, or SEQ ID NO: 24, or a sequence having at least 90% identity with any one of SEQ ID NO: 1, SEQ ID NO: 21, or SEQ ID NO: 24. Also a vector including a regulatory element having at least one copy of this miRNA target site of the miR183 family. The isolated nucleic acid sequence and the vector may be particularly useful for controlling the expression of a gene of interest, for example when designing and developing gene therapies.

The invention discloses a human zinc finger-truncated nucleus receptor fused small molecule response type gene regulation system and application thereof, and relates to the technical field of gene engineering. The gene regulation and control system contains transcriptional regulation and control protein, and the transcriptional regulation and control protein is formed by fusing a human zinc finger DNA binding module and a truncated nuclear receptor; the human zinc finger DNA binding module can specifically recognize and bind a target DNA regulatory sequence, and the truncated nuclear receptor is combined with a ligand to serve as a transcriptional regulatory module to realize controllable expression of a target gene; the human zinc finger DNA binding module is a human or humanized zinc finger array; according to the truncated nuclear receptor, an inherent DNA binding domain and an N-terminal transcriptional activation region are removed, and a hinge region and a ligand binding region are mainly reserved. The gene regulation system disclosed by the invention has the characteristics of humanization, compact structure, capability of being regulated by small molecules and the like, and in some embodiments, in-vivo or in-vitro controllable expression of a target gene can be realized.

Provided is a Phaeodactylum tricornutum TwOSC4 mutant (Pt-HYU-OSC4) that produces friedelin, and makes it easier to culture and extract friedelin from the strain, and thus can increase the productivity of friedelin to mass-produce and industrially use friedelin. The mutant is produced through a transformation process, can be a transformant or a mutant, and is a strain that includes a TwOSC4 (oxidosqualene cyclase derived from Tripterygium wilfordii) gene, in which the gene is under an expression regulatory sequence that enables its expression, and that has been transformed into Phaeodactylum tricornutum.

Provided herein is a method of treating a subject for a glioblastoma, the method comprising: administering to the subject an immune cell genetically modified with: (a) a nucleic acid sequence encoding a binding triggered transcriptional switch (BTTS) that binds to a priming antigen that is tissue-specifically expressed in the central nervous system; (b) a nucleic acid sequence encoding a tandem chimeric antigen receptor (CAR) or T cell receptor (TCR) that has a first binding domain that recognizes Ephrin type-A receptor 2 (EphA2) and a second binding domain that recognizes Interleukin-13 receptor subunit alpha-2 (IL13RA2); and (c) a regulatory sequence operably linked to (b) that is responsive to the BTTS, wherein binding of the BTTS to the priming antigen activates expression of the tandem CAR or TCR, which binds EphA2 and / or IL13RA2 in the glioblastoma and induces killing of glioblastoma cells.

This invention relates to a method and system for predicting insect multi-tissue expression levels based on multimodal feature fusion. Using the target gene as the basic prediction unit, it simultaneously inputs the target gene's regulatory sequence information, RNA stability characteristics, and protein representation information. Joint modeling is performed through a multi-tower deep learning network, outputting predicted expression levels of the target gene in multiple tissues. Advantages: It overcomes the limitations of traditional methods that primarily rely on single-modality data. For the first time, it integrates insect gene regulatory sequences, RNA stability features, and pre-trained protein language models into a unified expression prediction framework. Utilizing the multimodal prediction model, it extracts, fuses, and predicts multimodal data features, providing accurate and comprehensive gene expression level prediction results. Furthermore, it introduces a gating backoff mechanism for missing protein annotations, avoiding the misinterpretation of missing values ​​as zero or noise, thus ensuring prediction stability.

The present disclosure provides methods and compositions for modulating expression of a target gene in a cell by reducing binding of an endogenous transcription factor to a regulatory sequence of the target gene. The method includes introducing into the cell a DNA binding polypeptide (DBF) that binds a sequence in regulatory region of a target gene bound by a transcription factor (TF), thereby displacing the TF and modulating expression of the target gene. The DBF may be designed to bind a sequence comprising the binding site for the TF and additional nucleotides present on one or both sides of the sequence. Accordingly, the DBF specifically binds to binding site for the TF in the target gene but not in other genes that are also regulated by binding of the TF but do not include the nucleotides present on one or both sides of the sequence.

The invention provides a small molecule switch induced AAV8-tetracycline switch-hEPO (human erythropoietin) for treating anemia. Specifically, the invention provides a construction for inducing expression of a tetracycline regulatory sequence and a target gene (such as human erythropoietin (hEPO)), a vector containing the construction, a host cell, a gene delivery system, a pharmaceutical composition, a product combination and application of the construction in treatment of diseases (such as anemia). According to the invention, a wide application prospect is provided for accurate, controllable, changeable and customizable treatment, and the safety of gene treatment is improved. For example, under regulation and control of a tetracycline switch, the anemia treatment method provided by the invention has very high safety while effectively treating anemia, and the problems of serious and fatal polycythemia and the like caused by continuous increase of erythrocyte generation due to excessive production of EPO are avoided.

Aspects of the disclosure relate to compositions and methods for expressing a Factor H protein (or a variant thereof) in a cell or subject. In some embodiments, the disclosure provides isolated nucleic acids and rAAVs comprising a transgene encoding a Factor H protein variant and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with Factor H deficiency.