31results about "Nuclear receptor" patented technology

The present disclosure provides AAV vectors encoding modified chimeric ligand gated ion channels and methods for treating trigeminal neuralgia in a subject in need thereof.

The present invention relates to compositions and methods for treating cancer with chimeric antigen receptors.

To suppress growth of tumor cells and provide novel means for tumor treatment by inducing differentiation of tumor cells into mature cells by mediating overexpression of HNF4α in tumor cells by self-replicating RNA.SOLUTION: Provided is a gene delivery system comprising a nucleic acid vector and a delivery vehicle. Therein the nucleic acid vector is a self-replicating RNA carrying HNF4α; the gene delivery system delivers HNF4α into tumor cells and induces differentiation of the tumor cells into normal mature cells; the self-replicating RNA is based on one engineered alphavirus genome and has a polyadenylic acid tail of 35-100 nt; and the delivery vehicle is a lipid nanoparticle.SELECTED DRAWING: Figure 23

The present invention relates to the field of tumor immunology, and particularly relates to a gene editing-based animal model, for efficiently and rapidly screening for tumor antigen-specific B cells, obtaining antibody information, and providing a new target for clinical personalized treatment.

This invention provides a method for detecting 25-OH-VD using a VDR and RXRα double-sandwich method, comprising: sequentially synthesizing VDR and RXRα sequences, expressing VDR and RXRα, purifying VDR and RXRα; and using the purified VDR and RXRα proteins to detect the content of 25-OH-VD using the double-sandwich method. This invention provides a method for detecting 25-OH-VD content using a VDR and RXRα double-sandwich method, which solves the problems of low accuracy and narrow linear range in competitive methods for detecting 25-OH-VD content. Furthermore, this method is simple to operate, does not require animal immunization for antibody preparation, and saves preparation time and resources.

There remains a need in the art for the production and culture of mature adipocytes that are suitable for human consumption and can be produced in a scalable, cost-effective manner. The present invention relates to pluripotent stem cells comprising an expression construct for the expression of PPAR-γ protein and an expression construct for the expression of CEBPα protein. The present invention further provides a method for producing adipocytes comprising the pluripotent stem cells, and a food product comprising the adipocytes or the pluripotent stem cells.

Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non- alcoholic fatty liver disease (NAFLD) is the most common liver disease with a worldwide prevalence estimated at 30% of the general population. To better understand the influence of MASLD progression on cardiovascular disease, the aim of the study was to develop a new physiopathological mouse model able to develop progressive MASLD, along with atherosclerosis development, in a reasonable period of time. LDLr - / - mice were crossed with PPARα-deficient mice in order to obtain LDLr- / - mice expressing (LDLr - / - PPARα + / +) or not (LDLr - / - PPARα - / -) PPARα. Female mice were challenged with a high-fat diet during 12 and 18 weeks. Histological liver analysis showed that, compared to control diet, LDLr - / - PPARα + / + mice under high fat diet developed mostly steatosis at 12 weeks, and then exhibited all characteristics of human MASLD, namely the steatosis, inflammation and ballooning-triad, with presence of fibrosis at 18 weeks. This MASLD progression over time in LDLr - / - PPARα + / + was aggravated in LDLr - / - PPARα + / + mice. The present invenion defines a new relevant mouse model of progressive MASLD, developing all the characteristics of human MASLD (steatosis, inflammation, ballooning, fibrosis), in a relatively short time period (12-18 weeks), along with simultaneous atherosclerosis development.

Provided herein are binding molecules to tumor associated macrophages and associated methods for the treatment and detection of cancer.

The present disclosure provides polynucleotides that are capable of reducing the level of a NR4A3 gene and / or NR4A3 protein in a cell (e.g., immune cell). In some aspects, the polynucleotides comprises a gRNA that specifically targets a region within the NR4A3 gene. The present disclosure also provides the use of such polynucleotides to treat various diseases or disorders.

A gene delivery system and applications thereof in the technical field of biological medicines that is particularly useful in the preparation of drugs for treatment of tumors are disclosed. The gene delivery system and applications relate to technology for inducing the differentiation of malignant tumor cells into mature cells, in which regulating the expression of HNF4 alpha protein in the malignant tumor cells using messenger ribonucleic acid, the malignant phenotype of the malignant solid tumor cells is inhibited, and the effective treatment of the malignant solid tumors is achieved. The gene delivery system and applications are therefore applicable to a method of preparing a drug for treating malignant solid tumors and to a method of treating a patient having a malignant solid tumor.

The application discloses an application of a nuclear receptor target gene in preparation of a biological preparation for blocking activation of diapause larvae, and relates to the field of biotechnology and parasite prevention and control. According to two nuclear receptor targets of Haemonchus contortus HCON_00101910 (regulating activity of worms) and HCON_00023750 (regulating development of larvae), the two nuclear receptor targets are combined with host progesterone and estradiol and are activated, constitute a key signal path in the spring activation process of diapause larvae, and have no homologous genes in mammals, and the safety is excellent. By constructing specific shRNA lentivirus vectors (the silencing efficiency is all greater than or equal to 60%) targeting the two genes, single target or double target synergistic intervention is realized, and the activity-development double key links of worms in the host body can be specifically blocked. The application provides a new paradigm of preventive prevention and control with high specificity and green safety, and provides core technical support for solving the seasonal epidemic problem of blood fluke disease.

A novel technique for improving secretory production of a heterologous protein by coryneform bacteria is provided, and thereby a method for secretory production of a heterologous protein is provided. A coryneform bacterium having an ability of secretory producing a heterologous protein and having been modified so that an activity of a Mdh protein is reduced is cultured to produce the heterologous protein by secretory production.

An agent for treating a common form of autosomal dominant retinitis pigmentosa (ADRP) is disclosed, wherein the agent comprises a first nucleotide sequence encoding a CRISPR-associated (Cas) endonuclease which binds to an NG or NNGRRT PAM (protospacer adjacent motif) sequence, and a second nucleotide sequence encoding or comprising a guide RNA (gRNA) capable of forming a CRISPR-Cas complex with said Cas endonuclease, wherein the gRNA is specifically targeted to a target mutant allele selected from RHOP23H and NR2E3G56R.

To provide a composition comprising an epitope of a peptide that may elicit an immune response in a subject following administration.SOLUTION: Such a composition may comprise a nucleic acid. The composition may comprise a peptide. The method disclosed herein comprises a step of administering a composition comprising an epitope of a peptide to a subject in need thereof. In some of aspects, the composition disclosed herein comprises [a first plasmid comprising] a first nucleotide sequence encoding a first epitope of a first antigen expressed by a cell associated with breast cancer, and a second plasmid comprising a second nucleotide sequence encoding a second epitope of a second antigen expressed by a cell associated with breast cancer, where the first and second nucleotide sequences are located in one or more plasmids.SELECTED DRAWING: None

The application discloses a SjHNF4 polypeptide antibody, a preparation method and application. The preparation method comprises the following steps: downloading a SjHNF4 protein sequence, screening a polypeptide sequence, adding a cysteine at an N terminal, then performing polypeptide synthesis and purification, coupling to obtain a recombinant polypeptide, mixing the coupled polypeptide with Freund's complete adjuvant to obtain a mixture, immunizing a mammal by using the mixture, taking heart blood of the mammal and separating serum to obtain a polypeptide antibody. The polypeptide antibody is detected by using an ELISA method, and then the polypeptide antibody is purified by using a polypeptide affinity chromatographic column. Finally, the binding affinity of the antibody and the antigen is detected by Western Blot and immunofluorescence experiments. The polypeptide antibody obtained by the application has high purity (not less than 90%) and high titer (not less than 512000), and has good purity and immunogenicity, can satisfy various experimental requirements and has commercial value.

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.

A novel technique for improving secretory production of a heterologous protein by coryneform bacteria is provided, and thereby a method for secretory production of a heterologous protein is provided. A coryneform bacterium having an ability of secretory producing a heterologous protein and having been modified so that an activity of a Mdh protein is reduced is cultured to produce the heterologous protein by secretory production.

A gene delivery system and applications thereof in the technical field of biological medicines that is particularly useful in the preparation of drugs for treatment of tumors are disclosed. The gene delivery system and applications relate to technology for inducing the differentiation of malignant tumor cells into mature cells, in which regulating the expression of HNF4 alpha protein in the malignant tumor cells using messenger ribonucleic acid, the malignant phenotype of the malignant solid tumor cells is inhibited, and the effective treatment of the malignant solid tumors is achieved. The gene delivery system and applications are therefore applicable to a method of preparing a drug for treating malignant solid tumors and to a method of treating a patient having a malignant solid tumor.

The invention relates to in vivo methods and compositions for converting one cell type to another cell type. In particular, the invention relates to transdifferentiation of a cell to a photoreceptor cell, preferably a rod photoreceptor cell. In one aspect, the invention provides an in vivo method for reprogramming a source cell, the method comprising increasing the protein expression of one or more transcription factors, or biologically active fragments or variants thereof, in the source cell, wherein the source cell is reprogrammed to exhibit at least one characteristic of a target cell, wherein the source cell is a glial cell, the target cell is a photoreceptor cell; and the transcription factors are one or more of those selected from ASCL1, NEUROD1, NRL, NR2E3, RAX, RORB, OTX2, CRX and PAX6.

To provide methods for treatment and diagnosis of cancer.SOLUTION: There are described herein, molecules which preferentially bind to and target tumor associated macrophages (TAMs), and methods of treating cancer in a subject, including the step of administering pharmaceutical compositions thereof to the subject. In some embodiments, the TAM binding molecule is a cyclic peptide. The cyclic TAM binding peptide comprises a) CRVLRSGSC, or b) CRVLRSGSC with at least one conservative amino acid substitution.SELECTED DRAWING: Figure 1A

The invention relates to methods and compositions for the in vitro or in vivo converting one cell type to another cell type. Specifically, the invention relates to transdifferentiation of a cell to a cone photoreceptor cell. In one aspect, the invention provides a method for reprogramming a source cell, the method comprising increasing the protein expression of one or more transcription factors, or biologically active fragments or variants thereof, in the source cell, wherein the source cell is reprogrammed to exhibit at least one characteristic of a target cell, wherein the source cell is a glial cell, the target cell is a cone photoreceptor cell or cone-like photoreceptor cell; and the transcription factors are one or more of those selected from NEUROG2, CRX, RAX, RORA, NEUROD1, OTX2, ASCL1, PAX6, THRB, MEF2C, FOXP1 and ONECUT1.

This invention belongs to the field of genetic engineering technology, specifically relating to the application of nuclear receptors LXRs in regulating the anticancer activity of NK cells. This invention provides the application of nuclear receptors LXRs in the preparation of biomarkers for detecting the antitumor activity of NK cells, wherein the LXRs include LXRβ and / or LXRα; and LXRβ is expressed in the SLC9B2 signaling pathway. This invention reveals for the first time the role of nuclear receptors LXRs in regulating the anticancer activity of NK cells.

This invention provides a system for controlling viral replication in response to hypoxic environments and its application. The system comprises: a gene encoding a hypoxia-responsive element, a gene encoding a viral transcription factor recognition element, and one or more genes encoding viral repressor factors, connected sequentially. This allows the viral repressor factor, a product of the target gene, to be expressed under normal oxygen conditions, but expressed at low levels or not at all under hypoxic conditions, thereby enabling the oncolytic virus to exert its specific killing effect on cancer cells and improving the efficacy of oncolytic viruses in the treatment of hypoxic diseases such as solid tumors.

Methods are disclosed for treating end-stage liver failure in a subject that include administering to the subject a therapeutically effective amount of a recombinant mRNA encoding HNF4α isoform 2. The methods can include administering a lipid nanoparticle including the recombinant mRNA to the subject. Also disclosed are recombinant mRNA encoding an HNF4α isoform 1 or HNF4α isoform 2, and lipid nanoparticles include the recombinant mRNA. Methods are also for treating liver disease or end-stage liver failure in a subject that include administering to the subject a therapeutically effective amount of a recombinant mRNA encoding HNF4α isoform 1.

The present disclosure provides a method of generating AVC-like cell(s) or AVC-like cardiomyocyte(s) from cardiogenic mesoderm cells comprising incubating the cardiogenic mesoderm cells in an AVC cardiomyocyte induction medium comprising WNT2 and retinoic acid (RA) to obtain the AVC-like cell(s). Preferably, the AVC-like cell(s) express TBX3 and at least one of BMP2, MSX2 and TBX2.

The invention belongs to the field of fusion proteins, and particularly relates to a super positive charge polypeptide and NR4A1 truncated fragment fusion protein and application thereof. The amino acid sequence of the fusion protein IDR-SCP of the super positive charge polypeptide and the truncated fragment of the orphan nuclear receptor NR4A1 is as shown in SEQ ID NO. 2. On the basis of retaining the functional activity of the NR4A1 truncated fragment, the cell membrane penetration efficiency of the protein is effectively improved by fusing the cell penetrating peptide SCP, and the intracellular delivery effect of the functional fragment is remarkably improved. The IDR-SCP provided by the invention has the treatment effects of improving NASH mouse liver injury, inhibiting inflammation and degrading liver fibrosis.

The invention discloses application of a nuclear receptor target gene in preparation of a biological agent for blocking diapause larva activation, and relates to the field of biotechnology and parasite prevention and control. According to two nuclear receptor targets of haemonchus contortus HCON00101910 (regulating and controlling activity of polypide) and HCON00023750 (regulating and controlling development of larvae), the two nuclear receptor targets are respectively combined with host progesterone and estradiol and are activated, a key signal channel is formed in the diapause larva activation process in spring, no homologous gene exists in mammals, and the safety is excellent. By constructing a specific shRNA lentiviral vector (silencing efficiency is greater than or equal to 60%) targeting two genes, single-target or double-target collaborative intervention is realized, and activity-development double key links of polypide can be specifically blocked in a host. The invention provides a novel preventive prevention and control normal form which is high in specificity, green and safe, and a core technical support is provided for solving the problem of seasonal prevalence of the haemonchus disease.

The invention belongs to the technical field of rapid screening and toxicity evaluation of new pollutants, and discloses a PPAR gamma active substance screening method based on PPAR gamma / RXR alpha heterodimerization. The method is used for detecting the PPAR gamma agonistic / antagonistic activity of chemicals. Aiming at the problems of incomplete biological process simulation, low sensitivity and the like existing in the conventional common reporter gene screening method, the invention constructs a novel screening method: firstly, introducing a chaperone nuclear receptor RXR alpha, and constructing a screening method based on PPAR gamma / RXR alpha heterodimerization so as to more accurately simulate an in-vivo regulation mechanism; and secondly, a co-activation factor NCOA6 (PRIP) is innovatively introduced, the transfection quality is determined to be 50-200ng, and the signal response intensity of the reporter gene is effectively enhanced. Through the work, the lowest effect concentration (LOEC) of the PPAR gamma active substance screening method on the PPAR gamma positive substance rosiglitazone (ROSI) is reduced from 1 mu M to 10 nM, the EC50 value is reduced to 213.4 nM, and the sensitivities are improved by 2.7 times and 100 times respectively. The method is easy and convenient to operate and suitable for efficient and accurate detection of low-concentration PPAR gamma active substances in the environment.

Provided are gene-edited tumor-infiltrating lymphocytes and T cell receptor-engineered T cells, and a use thereof in immunotherapy. By means of knocking out an NR4A1 gene, an NR4A2 gene, and / or an NR4A3 gene in a tumor infiltrating lymphocyte or a T cell receptor-engineered T cell, the proliferation capability and anti-tumor capability of the tumor infiltrating lymphocyte or the T cell receptor-engineered T cell are enhanced.

The present invention relates to a composition for inhibiting alpha-synuclein aggregation and a method for inhibiting aggregation, more specifically, to a technology for inhibiting alpha-synuclein aggregation and phosphorylation by introducing Nurr1 and Foxa2 genes into brain cells and expressing them together. The composition according to the present invention has excellent effects of inhibiting the aggregation and phosphorylation of alpha-synuclein and can be used for the treatment and prevention of Parkinson's disease.