134 results about "Genetic disorder" patented technology

The present invention relates to peptides, in particular cell-penetrating peptides, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

The invention belongs to the technical field of gene editing, and discloses a base editor system and application. According to the invention, a heterologous peptide sequence is inserted into IscB protein, the obtained peptide embedded IscB is fused with deaminase or glycosylase to construct a base editor, and DNA base editing is carried out. According to the base editor system, the size limitation is overcome, and single AAV delivery is achieved; the editing efficiency is obviously improved; the broad-spectrum applicability is realized; the system optimization is more flexible; the method has efficient editing potential in vivo, and the off-target effect is reduced. The invention provides an important new strategy for hyperlipemia treatment and provides a basis for gene therapy of other hereditary diseases.

the present invention relates to peptides, in particular cell-penetrating peptides, having a first hydrophobic domain positioned at the C-terminus of the peptide and a second hydrophobic domain positioned at the N-terminus of the peptide, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' UTR-encoding region of genes encoding VGSC alpha subunits (NaV) to abrogate or create an upstream open reading frame (uORF). The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' splice acceptor site (SA) of an exon of a gene encoding a voltage-gated sodium channel (VGSC) alpha subunit (NaV). The invention also relates to use of the guide polynucleotides and methods for treating genetic disorders, in particular Dravet syndrome.

The present disclosure relates to compounds of Formula (I′):and to their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating orexin-2 receptor activity and may be used in the treatment of disorders in which orexin-2 receptor activity is implicated, such as narcolepsy, a hypersomnia disorder, a neurodegenerative disorder, a symptom of a rare genetic disorder, a mental health disorder, a metabolic syndrome, osteoporosis, cardiac failure, coma, or facilitating emergence from anaesthesia.

The present invention relates to a system and method configured for analysing acoustic parameters of speech to detect, diagnose, predict and / or monitor progression of a condition, disorder, or disease, and more particularly, any of paediatric and adult neurological and central nervous system conditions including but not limited to low back pain, multiple sclerosis, stroke, seizures, Alzheimer's disease, Parkinson's disease, dementia, motor neuron disease, muscular atrophy, acquired brain injury, cancers involving neurological deficits, paediatric developmental conditions and rare genetic disorders such as spinal muscular atrophy. The system and method extracts a first formant data set from words spoken by an individual and uses these to classify the vowels in the words on a first computing device, such as a mobile smart phone equipped with a microphone into which an individual speaks. The system stores at least some of these frequencies for the vowel formants in a second formant data set as a recorded file and provides the second formant data set as input to acoustic metrics to generate score data from which an assessment is made to determine the articulation level of the vowels in the words spoken by the individual, allowing allow for detection, diagnosis, prediction and / or monitoring progression of the condition, disorder, or disease.

This disclosure generally relates to super minimal transposon inverted repeat sequence (ITR) polynucleotides, compositions comprising the polynucleotides and methods of using compositions comprising the polynucleotides for the ex vivo and in vivo delivery of nucleic acids to cells, in particular, in vivo delivery of therapeutic genes to treat genetic disorders or diseases.

To provide an antisense oligonucleotide for preventing, delaying, and / or treating a human cis-element repeat instability-associated genetic disorder.SOLUTION: A medicament comprises, as an active ingredient, an oligonucleotide, wherein the oligonucleotide comprises 2'-O-methyl RNA nucleotide residues, has a backbone with at least one phosphate moiety being replaced by a phosphorothioate moiety, and comprises or consists of a repetitive nucleotide unit (XYG)m, wherein m is an integer from 4 to 12, each X is C or 5-methylcytosine, each Y is U or 5-methyluracil, and at least one X is 5-methylcytosine.SELECTED DRAWING: None

The invention relates to chemically modified oligonucleotides comprising a sequence with a length of 23 to 80 nucleotides, capable of binding to a target sequence in a target RNA, comprising a central base triplet (CBT) of 3 nucleotides (5′—N−1eN0fN+1g-3′) with the central nucleotide (N0) directly opposite to the target adenosine in the target RNA, wherein the core oligonucleotide comprises the following sequence: 5′—N−5aN−4b N−3cN−2dN−1eN0fN+1gN+2h N+3 iN+4j-3′ comprising different 2′ sugar and linkage modifications. The present disclosure also provides oligonucleotides and compositions thereof for use in use in the treatment or prevention of a genetic disorder, condition, or disease. Also provided are methods for editing a target adenosine or deaminating at least one specific adenosine in a target nucleic acid.

The invention provides improved methods for enriching targeted genomic regions of interest to be analyzed by multiplexed parallel sequencing. The methods of the invention utilize a pool of TArget Capture Sequences (TACS), wherein the pool comprises a plurality of TACS families, each member of a family binding to the same target sequence but with different start and / or stop positions on the sequence (i.e., staggered binding of the family members to the target sequence) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods of the invention can be used for a variety of clinical purposes, including non-invasive prenatal testing for chromosomal abnormalities, for example using a maternal blood sample or a sample of fetal cells, assessment of maternal and paternal carrier status for genetic disorders and detection of tumor biomarkers (e.g., liquid biopsy). Kits for carrying out the methods of the invention are also provided.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS. HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

The invention belongs to the field of pathologies affecting the central nervous system: in particular, severe cerebral pathologies, more particularly those restricted by the presence of the blood-brain barrier (BBB): gliomas, cerebral metastases, neurodegenerative diseases (e.g. Alzheimer's, Parkinson's or ALS), genetic diseases (Huntington's, myopathies, Leigh syndrome, Rett syndrome), but also to the field of cancers, musculoskeletal and immunological disorders, vascular diseases (thrombus) in numerous organs (e.g. liver, kidney or muscle) and in combination with numerous therapeutic approaches (e.g. chemotherapy, immunotherapy, targeted therapy or gene therapy). The invention relates to a microbubble comprising a fluorinated polymer or copolymer and a fluorinated gas, to the use thereof and also to the polymer or copolymer intermediate compounds.

The present invention relates to compositions and methods for subpopulation-specific modulation of cell function and for treating repeat expansion disorders comprising genetic, degenerative, neurological and cellular diseases, including immune disorders. Also provided are research kits for subpopulation-specific modulation of protein activity and the corresponding potential to discover novel therapeutic compositions. More specifically, the disclosed compositions and methods selectively up- or downregulate at least a first population of a cellular protein or therapeutic target with minimal or negligible effect on the activity of at least a second population of the cellular protein or therapeutic target.

The invention features the use of an adenylate deaminase base editor to destroy the scissor acceptor site of a disease-related gene, including compositions and methods for treating genetic diseases, particularly for treating, alleviating or ameliorating the asthenic effect of amyotrophic lateral sclerosis (ALS) and spinal bulbar muscular atrophy (SBMA). Provided herein are compositions and methods for using improved new base editors (e.g., adenosine base editors) comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain that cooperate with a guide polynucleotide, e.g., adenosine base editors, for example, adenosine base editors, for example, adenosine base editors, for example, adenosine base editors, for example, adenosine base editors, for example, adenosine base editors. The present invention relates to a method for modifying a target gene associated with a hereditary disease or disorder, such as ALS or SBMA, by modifying the target gene using a base editor system provided herein to disrupt normal transcription of a gene associated with the hereditary disease or disorder.

Systems, methods and computer-readable media are provided for identification of patients or family member having genetic disease or probable genetic disease. During or after registration of a patient, parents, grandparents, or siblings of the patient are identified. If it is determined that one of the patient or the parents, grandparents, or siblings of the patient has been assigned with a diagnosis indicating a genetic disease, an alert for genetic disease or probable genetic disease for the patient or family member of the patient is provided. A clinician is then prompted to confirm or rule out the patient or family member inheriting the disease.

The present disclosure provides compositions related to binding of various sarcoglycan proteins, which are relevant for their role in numerous genetic disorders, including limb girdle muscular dystrophy. The disclosure includes proteins, antibodies and / or fragments thereof and associated polynucleotide constructs. The disclosure further provides methods for manufacturing said compositions and other uses for the same.

A multi-chimeric cell created by ex vivo fusion of three or more hematopoietic stem cells, mesenchymal stem cells, myoblasts, pericytes, or satellite cells, or a combination thereof, from three or more different donors is provided, as is the use of these cells in transplant therapy and treatment of immune deficiency and genetic disorders.

Provided is a platform for expressing a protein of interest by artificially manipulating the liver, and more particularly, to a platform for alleviating or treating a genetic disorder or improving a body function by inducing expression by inserting a transgene (e.g., a therapeutic gene) which can function or be expressed normally, into a high-expression secretory gene, instead of a disease gene which functions or is expressed abnormally. The high-expression secretory gene includes the HP or APOC3 gene. The transgene includes one that is highly expressed using a promoter in a hepatocyte genome and is secretory out of the cell.

The invention discloses application of an adenine base editor in DFNA15 deaf mice, and belongs to the technical field of hearing loss treatment. The invention provides nine types of novel ABE fusion proteins, namely SchABE8e, SchABE8e-N108Q, SchABE9, SchABE8e, SchABE8e-N108Q and SchABE9. The reagent is composed of SpeABE8e, SpeABE8e-N108Q, SpeABE9, SpeABE8e, SpeABE8e-N108Q, the invention relates to the technical field of chemical engineering, in particular to the chemical engineering of Sha2ABE8e, Sha2ABE8e-N108Q, Sha2ABE9 and Sha2ABE8e-N108Q. The fusion protein comprises an SchCas9 nuclease nick enzyme and a TadA-8e deaminase, wherein the amino acid sequence of the SchCas9 nuclease nick enzyme is SEQ ID NO. 19, and the amino acid sequence of the TadA-8e deaminase is SEQ ID NO. The amino acid sequence of the TadA-8e deaminase is as shown in SEQ ID NO. 20. The invention provides a novel base editing tool with wide targeting range, high editing activity and smaller size, and provides more powerful support for gene therapy research of hereditary diseases. The screened SchABE8e base editor is comprehensively tested on an endogenous target spot, and the accurate and efficient editing performance of the SchABE8e base editor is verified through multiple dimensions such as editing efficiency, an editing window, product purity, indels and off-target activity. The wide targeting range of the editor enables the editor to be suitable for gene therapy research of various hereditary diseases.

The present disclosure provides a fusion protein useful for treating a non-nuclear organelle associated disorder, such as a genetic disorder, e.g., Friedrich's Ataxia. The fusion protein may comprise a protein of interest to be delivered to a non-nuclear organelle; an organelle targeting sequence (OTS); a cell penetrating peptide (CPP); and a target enhancing sequence (TES); wherein the CPP is capable of interference with delivery of the protein of interest to the non-nuclear organelle; and wherein the TES prevents interference by the CPP. The fusion protein may also comprise a protein of interest to be delivered to a non-nuclear organelle; a CPP and a TES. The present disclosure also provides methods for treating a non-nuclear organelle associated disorder by administering the fusion protein to a subject in need thereof.

The described technology pertains to gene therapy methodologies, specifically techniques and systems for delivering therapeutic genes of substantial size that exceed the packaging capacity of adeno-associated virus (AAV) vectors. The disclosed approach employs up to four AAV vectors and the CRE-lox DNA recombination system, utilizing novel lox site embodiments that allow sequence-specific and near-unidirectional recombination. This method supports efficient reconstitution of therapeutic genes up to 16 kb in a predetermined arrangement. Applications include the delivery of genes such as IFT140, PCDH15, CEP290, and CDH23 for addressing genetic disorders, including retinal degeneration. The described technology demonstrates successful production of full-length proteins in mammalian cells and mouse retinas, with therapeutic efficacy observed in an IFT140-associated retinitis pigmentosa mouse model. The CRE-lox approach offers a flexible platform for addressing AAV's packaging constraints, enabling effective gene therapy for large genes.

The present invention relates to a novel method of treating pulmonary emphysema in patients suffering from alpha-1 antitrypsin deficiency (AATD), a genetic disorder that causes low levels of alpha-1 antitrypsin (AAT), a protein that protects the lungs from damage by neutrophil elastase. The invention consists of aerosolizing nanoparticles composed of apolipoprotein A1 enriched with AAT (A1NP). The invention aims to deliver these nanoparticles directly to the lungs, where they can interact with the alveolar surface and modulate the inflammatory and proteolytic processes that lead to emphysema. In particular, the inventors report that said nanoparticles are not cytotoxic, have anti-inflammatory and anti-elastase properties, can cross alveolar epithelial cells, and are not immunogenic in mice.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and / or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

The present disclosure relates to an engineered hematopoietic cell comprising a very late antigen-4 (VLA-4) variant and uses thereof in treating an inherited genetic disorder or an acquired disorder.

The present invention relates to compositions and methods for molecular profiling and diagnostics for genetic disorders and cancer, including but not limited to gene expression product markers associated with cancer or genetic disorders. In particular, the present invention provides algorithms and methods of classifying cancer, for example, thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.

The invention provides a nucleic acid pharmaceutical composition of a gene editor and an anti-fibrosis inhibitor for disease treatment. Specifically, the pharmaceutical composition comprises: (a) a first active component which is a gene editor for performing base editing on a target gene; and (b) a second active ingredient, wherein the second active ingredient is an anti-fibrosis inhibitor. According to the present invention, the hereditary disease is treated by using the nucleic acid sequence encoding the gene editor and the anti-fibrosis inhibitor through the virus or non-virus vector system, such that the fibrosis signal in the microenvironment can be inhibited while the gene is repaired so as to achieve the synergistic treatment effect.

The present invention relates to substituted benzyl piperidines of Formula (I) as well as to their use as TRPV4 antagonists for use in treating e.g. inflammatory, respiratory, metabolic, dermatological, skeletal, neuromuscular or genetic diseases or disorders, cancer, or pain.