31 results about "Hereditary Diseases" patented technology

Provided herein are elastin-like polypeptides, endosomal escape peptides, and compounds comprising an elastin-like polypeptide chemically or recombinantly conjugated to one or more endosomal escape peptides. Also provided herein are compositions comprising a compound provided herein and an agent, methods of delivering an agent, and methods of treating or preventing a disease (e.g., a cardiovascular disease, a lung or respiratory disease, a musculoskeletal disease, a hematological disease, an immune disorder, an infectious disease, a genetic disease, cancer, a neurological disease, a psychiatric disorder, a metabolic disorder, or an inflammatory disease).

The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

The invention relates to a compound according to general formula (I), which acts as a bradykinin (BK) B2 receptor antagonist; to a pharmaceutical composition containing one or more of the compound(s) of the invention; to a combination preparation containing at least one compound of the invention and at least one further active pharmaceutical ingredient; and to said compound(s) for use as in a method of treating a skin disorder; eye disease; ear disease; mouth, throat and respiratory disease; gastrointestinal disease; liver, gallbladder and pancreatic disease; urinary tract and kidney disease; disease of male genitale organs and female genitale organs; disease of the hormone system; metabolic disease; cardiovascular disease; blood disease; lymphatic disease; disorder of the central nervous system; brain disorder; musculoskeletal system disease; allergy disorder; pain; infectious disease; inflammatory disorder; injury; immunology disorder; cancer; hereditary disease; or edema.

The present invention relates to a novel lipid compound for tissue-specific delivery, and a lipid nano-particle (LNP) composition comprising the same, the lipid nano-particle comprising a modified lipid compound as a component, according to the present invention, internal active substances are selectively delivered into cells of specific tissues such as lymph nodes, spleen, retina, cancer, brain, liver and the like in vivo, thereby preventing side effects and safely exhibiting a desired level of effect. The tissue-specific non-viral LNP delivery vectors can be effectively used for prevention of infectious diseases and treatment of rare and refractory (hereditary) diseases (diseases which are effectively and selectively delivered to in-vivo targeted sites, such as macular degeneration, diabetic retinal degeneration, hereditary retinal degeneration, cancer, cerebral diseases, liver diseases and the like).

The present disclosure relates to Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), an autosomal dominantly inherited neurodegenerative disorder that is caused by an over-repetition of the polyglutamine-codifying region in the ataxin-3 (ATX7V3) gene. Expanded ATXN3 is prone to aggregate and disturbs diverse cellular systems, ultimately leading to cell dysfunction and death in specific neuronal populations. To date, no treatment able to reverse or stall MJD / SCA3 progression has been developed. Strategies based on the suppression of the deleterious gene products have demonstrated promising results in pre-clinical studies. Nonetheless, these strategies do not target the root cause of the disease, producing an incomplete and / or transient therapeutic effect in target cells or tissues. Recently, gene-based therapeutics, including the bacterial clustered regularly interspaced short palindromic repeat (CRISPR) systems for gene edition, have been successfully used to permanently inactivate and correct disease-related genes, holding promise for the development of a definitive cure for inherited diseases.

The present invention provides a lipid material for nucleic acid delivery, wherein the lipid material comprises a compound having structure I. The present invention also provides use of the lipid material for nucleic acid delivery in the preparation of a therapeutic drug for one or more selected from an infectious disease, a tumor disease, a congenital hereditary disease, and an immune disease. By means of the lipid material provided in the present invention and adopting a nucleic acid drug carrier strategy with high efficiency and low toxicity, a novel ionizable lipid and an auxiliary lipid material are mixed to encapsulate nucleic acid drugs, so that efficient and safe delivery of the nucleic acid drugs in vivo is achieved, and the druggability of the nucleic acid drugs is improved.

The invention relates to the technical field of gene detection, in particular to a probe composition and a kit for screening various genetic disease related gene mutations and a preparation method of the probe composition and the kit. The hereditary diseases comprise 23 hereditary diseases such as citrullinemia type, hepatolenticular degeneration, 21-hydroxylase deficiency, progressive pseudohypertrophy muscular dystrophy, fragile X syndrome, Friedreich ataxia, glycogen accumulation disease type II, Gaucher disease, autosomal recessive deafness type 1A, Fabry disease, alpha-thalassemia, beta-thalassemia and the like. The probe composition disclosed by the invention can be used for simultaneously screening the specific mutation types of the various genetic disease related genes, and is more accurate, comprehensive, convenient, high in detection efficiency, simple and economical compared with the traditional screening.

The present invention provides a method for evaluating the risk of developing a hereditary disease in an individual by a variant of uncertain clinical significance (VUS), the method comprising: introducing DNA for a genetic factor for a hereditary disease, including at least one VUS, into a fertilized egg of zebrafish under the control of a promoter of a gene involved in a phenotype; and evaluating the risk of developing the hereditary disease by the VUS, by observing the change in the phenotype in the zebrafish.

Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions / disorders / diseases due to mutations or dysregulation of the Wnt pathway and / or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Disclosed herein are methods and systems ofscreening for microbiomics treatments for hereditary diseases or metabolic diseases using high-throughput nematode models. Genetically modified bacteria with therapeutic potential in treating certain hereditary diseases or metabolic diseases, compositions comprising such bacteria, as well as methods of uses such bacteria are also disclosed herein.

A method for constructing a classifier to classify variants of uncertain significance (VUS) is proposed according to the present disclosure, wherein raw data collected from databases comprising public Mendelian and hereditary disease RNA-Seq and / or DNA-Seq data is used for training a random forest model. Training data is based on a feature table created using variant analysis based on difference to reference genome, variant annotation based on at least multiple measures, RNA-Seq expression analysis, as well as RNA-Seq splicing analysis. A system for classifying the pathogenicity of variants of uncertain significance based on the disclosed method is also disclosed according to the present disclosure.

The invention belongs to the field of medicines, and particularly relates to a nitrogen-containing heteroaromatic ring degradation agent as well as a preparation method and application thereof. Particularly, the invention relates to a compound as shown in a general formula (I), a preparation method thereof and a pharmaceutical composition containing the compound, the invention also relates to the application of the compound in preparation of medicines for treating or preventing autoimmune diseases, inflammatory diseases, cancers, viral diseases, neurodegenerative diseases, hereditary diseases, hormone-related diseases, metabolic diseases, organ transplantation-related diseases, immunodeficiency diseases, destructive bone diseases, proliferative diseases, infectious diseases and the like. The invention also relates to the application of the medicine for treating diseases related to cell death or cardiovascular diseases. Wherein each substituent in the general formula (I) is as defined in the specification.

The present invention discloses a method for preparing a tumor microenvironment responsive cascade-targeted small activated nucleic acid nanomedicine and its application, and belongs to the field of biomedicine technology. The present invention utilizes the dendritic macromolecule PAMAM modified with M2 type TAM targeting peptide CRVLRSGSC to jointly load the small activated RNA (sa-p38, sa-TFEB) of p38 and TFEB, and uses acid-sensitive liposomes to encapsulate and protect the above-mentioned complex (CRV-PAMAM / saRNA) to prepare tumor microenvironment responsive cascade-targeted small activated nucleic acid nanomedicine, which can reprogram the phenotype and metabolic mode of M2 type TAM to M1 type TAM, thereby killing tumor cells, and remodeling the tumor immune microenvironment, ultimately inhibiting tumor growth and even ablating tumors. The present invention has a very broad application prospect in gene therapy and immunotherapy for cancer, hereditary diseases, infectious diseases, etc.

The invention relates to a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) mediated gene transcription activation (CRISPRa) system and an application thereof, and preferably relates to a gene transcription activation system (miniCRISPRa system) based on miniCas and an application thereof. According to the present invention, the small Cas protein and the transcriptional activation structural domain VP64 are adopted, and the multimerization peptide fragment is adopted to rapidly collect the large amount of VP64 to the target gene, such that the miniCRISPRa system with characteristics of small molecular weight, high efficiency, no preference and easy delivery is developed so as to achieve the efficient transcriptional activation of the target gene; the invention also relates to an application of the CRISPRa system in treating hereditary diseases and tumors or delaying senescence.

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions / disorders / diseases due to mutations or dysregulation of the Wnt pathway and / or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

The invention provides a probe composition, a gene chip, a reagent, a kit and application. The probe composition is designed based on capture areas of 34 genes related to dominant single-gene genetic diseases, can be used for non-invasive prenatal genetics screening, and is suitable for prenatal screening of genetic variation positive family history, bad fertility history, fetal ultrasound examination abnormality, pregnant woman elderly, father elderly and the like. The omission ratio and the birth rate of fetuses suffering from the dominant single-gene hereditary disease are effectively reduced.

Disclosed in the present invention are an RNA replicon for improving gene expression, and a use thereof. The RNA replicon comprises: 5′ and 3′ untranslated regions; a non-structural protein gene coding region, a subgenomic promoter and a target gene coding region. In the present invention, a PCR site-directed mutagenesis technique is used to introduce the non-structural protein region mutant replicable RNA, which is transfected into mammalian eukaryotic cells by means of Lipofectamine 2000 or nanoparticles, so as to significantly enhance the expression of cytokines and chemokines including GM-CSF, IFN-γ, IL-2, IL-12, IL-15 mediated by downstream subgenomic promoters, and can be applied to treatment of tumors, infectious diseases, autoimmune diseases, hereditary diseases or cardiovascular diseases.

This invention relates to an IRAK4 degrading agent and its uses. This degrading agent can be used to treat or prevent diseases such as cancer, neurodegenerative diseases, viral diseases, autoimmune diseases, inflammatory diseases, hereditary diseases, hormone-related diseases, metabolic diseases, organ transplant-related diseases, immunodeficiency diseases, destructive bone diseases, proliferative diseases, infectious diseases, cell death-related conditions, thrombin-induced platelet aggregation, liver diseases, pathological immune conditions involving T cell activation, cardiovascular diseases, or CNS diseases.

The invention relates to a targeted protein degradation compound as well as a preparation method and application thereof, and belongs to the field of medicines. Specifically, the invention relates to a compound as shown in a general formula (I), a preparation method thereof and a pharmaceutical composition containing the compound, the invention also relates to the application of the compound in preparation of medicines for treating or preventing autoimmune diseases, inflammatory diseases, cancers, viral diseases, neurodegenerative diseases, hereditary diseases, hormone-related diseases, metabolic diseases, organ transplantation-related diseases, immunodeficiency diseases, destructive bone diseases, proliferative diseases, infectious diseases and the like. The invention also relates to the application of the medicine for treating diseases related to cell death or cardiovascular diseases. Wherein each substituent in the general formula (I) is as defined in the specification. B-L-K (I)

This disclosure provides isolated nucleic acid molecules comprising nucleic acid sequences encoding microbial polypeptides that are codon optimized for expression in mammalian cells, vectors comprising an immunotolerant dual promoter system, and methods using these polynucleotides and polypeptides to treat glycogen storage diseases and other inherited diseases.

The present disclosure provides a medicine for treating or preventing a hereditary disease, etc. The present disclosure provides a medicine for altering, preventing, or treating a condition, disease, disorder or symptom, which is caused by a frame-shift mutation due to the insertion or deletion of one or more bases, by cleaving at least one a target nucleic acid sequence in a nucleic acid within a cell, said medicine comprising a vector. This vector contains a construct that contains a promoter specific to the cell, a sequence encoding a Cas nuclease, a promoter enabling the expression of a gRNA in the cell after the introduction of the vector, and a sequence encoding a gRNA that binds to a target nucleic acid sequence having the insertion or deletion. This construct is configured so as to form a cleavage site, by the Cas nuclease, in proximity to the target nucleic acid sequence having the insertion or deletion.

The present invention provides a bionic nano delivery system and its preparation method and application, which belongs to the technical field of pharmaceutical preparation. The bionic nano delivery system in the present invention is composed of a black phosphorus nano sheet core and an M1 type macrophage membrane that wraps the black phosphorus nano sheet core, and has a photothermal effect under near-infrared light 780nm~1000nm laser irradiation. The present invention also provides a preparation method and application of the bionic nano delivery system. The bionic nano delivery system of the present invention can actively identify tumor cells and accumulate in cancer cells. After entering the cells, the local tumor tissue is rapidly heated under 808nm laser irradiation, ablating cancer tissue, and accurately and efficiently releasing drugs at the same time, causing cancer cell apoptosis, thereby inhibiting tumor growth. Therefore, the present invention has a very broad application prospect in thermal therapy, chemotherapy, imaging and / or treatment of cancer, hereditary diseases and infectious diseases.

This disclosure relates to Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3), an autosomal dominant neurodegenerative disorder caused by excessive repetition of the polyglutamine-coding region in the ataxia protein-3 (ATXN3) gene. The extended ATXN3 readily aggregates and interferes with multiple cellular systems, ultimately leading to cellular dysfunction and death in specific neuronal populations. To date, no treatments have been developed that can reverse or delay the progression of MJD / SCA3. Strategies based on inhibiting harmful gene products have shown promising results in preclinical studies. However, these strategies do not target the root cause of the disease, producing incomplete and / or transient therapeutic effects in target cells or tissues. Recently, gene-based therapies, including the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system for gene editing, have been successfully used to permanently inactivate and correct disease-related genes, offering hope for the development of curative therapies for hereditary diseases.

The present disclosure relates to compositions and methods for the detection, identification, sequence analysis and quantification of organisms in a single amplification reaction. The disclosed methods use next generation sequencing (NGS) to sequence the amplification products. The disclosure also relates to kits containing primers specific for microorganisms and viral organisms, cancer, genetic diseases, and forensic medicine.

The invention discloses a novel adeno-associated virus variant library for gene and cell therapy as well as construction and application of the novel adeno-associated virus variant library, and belongs to the field of biological medicines. Through high-throughput sequencing and gene editing, an AAV variant library containing a large number of mutants is constructed, the construction efficiency is improved, the diversity of the mutants is ensured, the cap gene of AAV is modified by the variant library through a site-directed mutagenesis technology, the transduction efficiency of human immune cells is improved, the limitation of an existing AAV modification method is overcome, and the AAV mutant library has good application prospects. The constructed novel AAV variant library has higher packaging efficiency, lower cytotoxicity and better adaptability, and provides more choices for development of gene therapy drugs; the screened novel AAV6 variant P482L has remarkable advantages in the aspects of transduction efficiency, safety and the like, and becomes a potential candidate vector in the field of gene therapy; the invention not only accelerates the progress of new drug research and development, but also provides a new tool and method for treating hereditary diseases, tumors and the like, and promotes the development of the field of gene therapy.

The invention provides a method for constructing a transmitochondrial human umbilical vein endothelial cell model, which is characterized in that a human umbilical vein endothelial cell is cultured by using an inhibition culture medium containing rhodamine 6G to inhibit the mitochondrial DNA replication of the human umbilical vein endothelial cell. And fusing the human umbilical vein endothelial cells with mitochondrial DNA deletion with donor mitochondria (immortalized lymphocyte source) carrying pathogenic mutation or normal control, thereby obtaining the transmitochondrial human umbilical vein endothelial cell model carrying mitochondrial DNA mutation. The method disclosed by the invention is high in operability, high in repeatability among batches and convenient for analyzing disease manifestations. The transmitochondrial human umbilical vein endothelial cell carrying pathogenic mutation, which is constructed by the method disclosed by the invention, provides a good model for researching maternal hereditary diseases related to vascular endothelial injury. The method has important research and application values in the aspects of vascular endothelial injury related mitochondrial disease pathological mechanism research, treatment method exploration, drug target discovery and the like.

This article specifically provides an expression system capable of regulating the expression of target genes. In an embodiment, the expression system silences the expression of the endogenous form of the gene and induces the expression of a recombinant form of the gene. The expression system provided herein is intended to be effective in treating hereditary diseases.

The invention relates to an IRAK4 degradation agent and application thereof. The degrading agent can be used for treating or preventing cancer, neurodegenerative diseases, viral diseases, autoimmune diseases, inflammatory diseases, hereditary diseases, hormone-related diseases, metabolic diseases, diseases related to organ transplantation, immunodeficiency diseases, destructive bone diseases, proliferative diseases, infectious diseases, conditions related to cell death, and the like. Thrombin-induced platelet aggregation, liver diseases, pathological immune conditions involving T cell activation, cardiovascular diseases or CNS diseases, etc.

Disclosed in the present invention are a method and a system for monitoring neonatal neurodevelopment. The method comprises the following steps: on the basis of a prediction model, predicting the probability of neurodevelopmental damage to a neonate caused by placental methylmercury, wherein independent variables of the prediction model comprise: placental methylmercury level, maternal age, maternal ethnicity, maternal dietary intake frequency of freshwater products, maternal denture installation during pregnancy, paternal genetic history, family history of hereditary diseases, paternal smoking status, occupational mercury exposure, Apgar score of the neonate at 1 minute, newborn congenital malformations, birth season, and placental weight, and on the basis of same, predicting the probability of the neonate having a neurodevelopmental disorder. The prediction model provided in the present invention has good discrimination, consistency and stability, and thus is an effective prediction model for monitoring neonatal neurodevelopment.