23 results about "Dominant negative" patented technology

Disclosed are compositions comprising dominant negative chimeric tumor necrosis factor receptor 1 (TNFR1) fusion proteins and methods for use in cell therapies.

The method as disclosed herein utilizes a high throughput screening assay (GigaAssay) to produce a comprehensive mutation effect on gene activity (MEGA)-mutation activity profile (Map). The methods as disclosed herein can be used to assess the mutational effect for any gene, under any condition (e.g., drug treatment) with any assay in mammalian cells in culture. Thus, the methods provided herein can be utilized to discover and screen dominant negative variants, and provide a reliable solution to the problem of identifying unique pharmacologically active variants of proteins. Furthermore, the method provided herein can be integrated to cell-based assays to investigate disease pathology and test potential drugs.

To provide, in part, methods and compositions for selectively editing a genome to create a dominant negative allele or a dominant positive allele.SOLUTION: The present disclosure provides methods and compositions for generating dominant alleles using targeted editing technologies. Also provided are modified chromosomes, cells, tissues, and plants comprising a modified dominant allele.SELECTED DRAWING: Figure 1

Disclosed are compositions comprising dominant negative chimeric tumor necrosis factor receptor 1 (TNFR1) fusion proteins and methods for use in cell therapies.

The invention discloses a promoter Mig6p induced by pathogenic bacteria and application of the promoter Mig6p in rice disease resistance improvement, and belongs to the technical field of phytopathology and genetic engineering. According to the invention, a rice promoter Mig6p (the nucleotide sequence is as shown in SEQ ID NO.1) induced by various pathogenic bacteria is screened; the Mig6p background expression activity is very low, and the Mig6p is not induced by various abiotic stresses. According to the Mig6p: Lrd6-6E315Q rice expression vector, Mig6p starting lesion-like gene Lrd6-6 dominant negative regulation mutant Lrd6-6E315Q expression vectors are constructed, Mig6p: Lrd6-6E315Q rice is obtained through rice transformation, and verification shows that the broad-spectrum disease resistance of the Mig6p: Lrd6-6E315Q rice is remarkably improved, and the agronomic traits are not obviously influenced. The invention provides important guidance for improving the disease resistance of crops by using the scab-like gene, and also provides reference for improving other similar characters.

The invention discloses a promoter Mig4p induced by pathogenic bacteria and application of the promoter Mig4p in rice disease resistance improvement, and belongs to the technical field of phytopathology and genetic engineering. According to the invention, a rice promoter Mig4p (the nucleotide sequence is as shown in SEQ ID NO.1) induced by various pathogenic bacteria is screened; the background expression activity of the Mig4p is very low. According to the Mg4p: Lrd6-6E315Q rice, the Mg4p: Lrd6-6E315Q rice is obtained by transforming the rice, the broad-spectrum disease resistance of the Mg4p: Lrd6-6E315Q rice is remarkably improved, and the agronomic characters of the Mg4p: Lrd6-6E315Q rice are not obviously influenced. The invention provides important guidance for improving the disease resistance of crops by using the scab-like gene, and also provides reference for improving other similar characters.

The invention discloses a promoter Mig1p induced by pathogenic bacteria and application of the promoter Mig1p in rice disease resistance improvement, and belongs to the technical field of phytopathology and genetic engineering. According to the invention, a rice promoter Mig1p (the nucleotide sequence is as shown in SEQ ID NO.1) induced by various pathogenic bacteria is screened; the background expression activity of the Mig1p is very low. According to the Mig1p: Lrd6-6E315Q rice expression vector, a Mig1p starting lesion-like gene Lrd6-6 dominant negative regulation mutant Lrd6-6E315Q expression vector is constructed, Mig1p: Lrd6-6E315Q rice is obtained through rice transformation, and verification shows that the broad-spectrum disease resistance of the Mig1p: Lrd6-6E315Q rice is remarkably improved, and the agronomic traits are not obviously influenced. The invention provides important guidance for improving the disease resistance of crops by using the scab-like gene, and also provides reference for improving other similar characters.

The present invention relates to a population of small extracellular vesicles (sEVs) for use in the treatment of obesity in a subject in need thereof, wherein the sEVs comprise at least one polynucleotide encoding a D168A dominant negative AMP-activated protein kinase alpha 1 (AMPKa1-DN) mutant protein operably linked and under the control of a steroidogenic factor 1 (SF1) promoter, wherein the sEVs are engineered to transiently express in their outer membrane at least one fusion protein comprising the neurotrophic rabies virus (RVG) peptide fused to lysosome-associated membrane protein 2b. Said population is highly safe and effective, as the sEVs, when administered systematically, are capable of exerting their effect in the SF1 expressing neurons located in the ventromedial nucleus of the hypothalamus.

The invention relates to nucleic acids encoding dominant negative polypeptides comprising the a3 helix of CC2 region and the SUN domain of a SUN domain-containing protein that inhibit the LING complex. The specific embodiment relates to polypeptides of varying lengths derived from amino acids 404-812 of SUNI with a KDEL signal sequence. It also relates to methods of identifying a LING complex inhibitor and the use of said polypeptides for treating and preventing laminopathies, and diseases characterised by hyperlipidaemia.

The invention discloses a WASF1 mutation pathogenic mechanism model construction and lead compound screening method, and belongs to the field of biological medicine. The problem that the WASF1 gene c.1516Cgt can be solved; the pathogenic mechanism of T truncation mutation is not clear; and targeted drugs are lacked. According to the technical scheme, the method comprises the following steps: comparing the non-phenotypic mutation of the c.873delA of the WASF1 gene with the non-phenotypic mutation of the c.1516Cgt of the WASF1 gene; determining a pathogenic mechanism as a dominant negative effect or function acquisition mechanism according to a protein expression mode of T pathogenic mutation; on the basis of the mechanism, a multi-parameter optimization Python script is adopted to call AutoDock Vina to perform batch virtual screening on the ZINC20 database small molecule compounds; by combining a comprehensive scoring system of energy score (40%), ADMET score (30%) and dynamic stability score (30%), a lead compound targeting the WASF1 mutant protein is screened out. The method is suitable for mechanism research and drug development of WASF1-related neurodevelopmental disorder diseases.

A composition including modified ASFV outer-membrane protein antigen mutants (termed dominant negative toxoid antigens) that exhibit non-binding affinity to RBCs while inducing an antibody-mediated response capable of neutralizing unmodified proteins found on infectious outer-membrane-laden ASFV virions. A method for the treatment and / or prevention of ASFV by administering a dominant negative toxoid antigenic composition to animals, thereby averting RBC aggregation caused by the antigen and concurrently treating and / or preventing ASFV. An ASFV vaccine composition including dominant negative toxoid antigens. A composition including dominant negative toxoid antigens in conjunction together and in conjunction with antigens derived from capsid-based proteins, which collectively target both lysogenic and lytic viral replication cycles, thereby achieving optimal immune stimulatory protection. Methods and compositions allowing for differentiation of infected from vaccinated animals (DIVA).

This invention discloses the soybean dominant negative-effect allele Gmspp-D and its application. Two dominant negative-effect alleles Gmspp-D (Gmspp-D-CDS-1 and Gmspp-D-CDS-2) regulating soybean pubescence density were cloned and overexpression vectors were constructed. Stable overexpression lines were obtained by transforming these vectors into the soybean cultivar Williams82 (W82). Compared to the control material W82, overexpression of both dominant negative-effect alleles significantly reduced soybean pubescence density, thus validating the function of the target genes. This invention provides the application of the soybean dominant negative-effect allele Gmspp-D in regulating plant pubescence density and demonstrates the feasibility and efficiency of constructing dominant negative-effect mutants for rapid gene function studies, showing promising application prospects in the field of breeding technology.

The present disclosure provides a modified immune cell or a precursor thereof (e.g., a T cell) comprising a first chimeric antigen receptor (CAR) capable of binding to human IL13R [alpha] 2, a second CAR capable of binding to EGFR or an isoform thereof, and a dominant negative TGFRII receptor (DN-TGFRII). Compositions and methods of treatment are also provided.

There is provided a therapeutic nucleic acid capable of binding to a target indel allele associated with a pathogenic allele, wherein the pathogenic allele causes a dominant negative genetic disorder or gain-of function genetic disorder, and wherein the disorder is not Huntington's disease. There is further provided a conjugate, delivery particle, and pharmaceutical composition thereof and their uses. There is further provided a therapeutic nucleic acid which is capable of binding to a target indel allele of an intronic indel selected from: rs59464879, rs751205475 and rs78373442 associated with a pathogenic HTT allele which causes Huntington's disease, and uses thereof.

The present disclosure is directed to an engineered protein (e.g., a chimeric protein) comprising one or more of an extracellular domain, a transmembrane domain and / or an intracellular domain, which are capable of binding a negative signal and functioning as a sink, dominant negative, or signal inverter for the negative signal. The disclosure is further directed to methods of generating a modified cell expressing one or more of the engineered proteins (e.g., chimeric proteins), and methods of using the modified cells in treating a disease or a condition in a subject in need thereof.

Dominant negative forms of CEBPB and CEBPD, and cell-penetrating forms thereof are described. Methods for using the dominant negative forms of CEBPB and CEBPD proteins, and cell-penetrating forms thereof, for decreasing viability of neoplastic cells and treating cancer in a subject are also described.

A composition including modified ASFV outer-membrane protein antigen mutants (termed dominant negative toxoid antigens) that exhibit non-binding affinity to RBCs while inducing an antibody-mediated response capable of neutralizing unmodified proteins found on infectious outer-membrane-laden ASFV virions. A method for the treatment and / or prevention of ASFV by administering a dominant negative toxoid antigenic composition to animals, thereby averting RBC aggregation caused by the antigen and concurrently treating and / or preventing ASFV. An ASFV vaccine composition including dominant negative toxoid antigens. A composition including dominant negative toxoid antigens in conjunction together and in conjunction with antigens derived from capsid-based proteins, which collectively target both lysogenic and lytic viral replication cycles, thereby achieving optimal immune stimulatory protection. Methods and compositions allowing for differentiation of infected from vaccinated animals (DIVA).

The present invention relates to modified Cas9 nuclease comprising a substantial part of a Cas9 nuclease and fused thereto at least one substantial part of a dominant negative effector on non-homologous end-joining selected from the group consisting of RNF168, 53BP1, Ku80 and DNA-PK which compete with NHEJ promoting factors and CtIP.

Compositions and methods for reducing one or more symptoms associated with fibrosis are disclosed. The compositions include one or more agents that inhibit SUN2 expression or activity, directly, or indirectly. The composition includes one or more functional nucleic acids that inhibit the production or stability of SUN2, CTDNEP1, and / or NEP1R1. In some forms, the compositions include a dominant negative protein or peptide to disrupt SUN2 function, including dominant negative truncations of Sun or Nesprin proteins In some forms the composition is a gene editing composition targeting SUN2, CTDNEP1, and / or NEP1R1. The compositions can include nucleic acids and / or small molecule activators that increase expression of CK2. The compositions can be administered to a subject in need thereof to treat one or more conditions in which fibrosis is implicated.

Provided herein are nucleic acids containing dominant negative STING alleles and compositions containing the same. Further provided are methods of using the nucleic acids containing dominant negative STING alleles for treating STING-associated vasculopathy with onset in infancy (SAVI). Also provided are methods of delivering the nucleic acids containing dominant negative STING alleles to treat STING-mediated conditions or diseases in human subjects in need thereof.

Provided herein are recombinant Herpes Simplex Virus-2 comprising sequences encoding glycoprotein D and B antigens, with two sequences encoding dominant negative UL9 proteins, compositions comprising the same, and methods of use thereof.