69 results about "Genetic disorder" patented technology

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 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.

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 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.

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 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.

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.

Provided herein are prime editing methods and compositions for treatment of genetic disorders such as Friedreich ataxia.

5′-O-Phenylacetyluridine effectively delivers both phenylacetate and uridine to a subject. It can be used to treat hepatic encephalopathy and genetic disorders of the hepatic nitrogen cycle.

The present invention relates to peptides, in particular cell penetrating peptides, of 40 amino acid residues or less comprising at least one directly glycosylated amino residue and one or more arginine rich arm domains, and to conjugates of such cell penetrating peptides with a therapeutic molecule. The present invention further relates to the use of the peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders of the central nervous system.

The present disclosure relates to compositions and methods for detection, identification, sequence analysis and quantification of biological organisms in a single amplification reaction. The disclosed method utilizes next-generation sequencing (NGS) to sequence amplified products. The present disclosure is also directed to kits containing primers specific to microbial and viral organisms, cancer, genetic disorders and forensics.

The present invention provides a composition comprising: a first single-stranded nucleic acid molecule comprising a region complementary to a target and a transposase recognition site; a second single-stranded nucleic acid molecule comprising a region complementary to the target and a transposase recognition site; and a third single-stranded molecule comprising a sequence encoding a portion of the interleukin-2 gamma receptor (IL2-Rγ) or encoding the entire IL2-Rγ receptor, and a transposase binding site.

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 relates to a hereditary disease MLPA detection data processing method and system, and the method comprises the steps: carrying out the quality control and standardization processing of multi-batch MLPA original peak graph data, constructing a unified data set, and employing a parallel double-engine analysis architecture: a non-time-series analysis engine processes extreme unbalanced data through an integrated learning framework, and carries out the processing of the extreme unbalanced data through the integrated learning framework; a key probe is screened in combination with a mixed feature selection algorithm, and a prediction result based on single detection is output; and the time sequence modeling analysis engine constructs the previous detection of the patient into an irregular time sequence, performs modeling on irregular intervals by using a multi-time attention network, fuses historical information through an attention mechanism, and outputs a prediction result based on time sequence dynamics. And synthesizing double-engine results through a decision fusion algorithm to generate a standardized detection report. According to the method, the detection rate of the rare variation and the reliability of the diagnosis result are remarkably improved, and the depth and accuracy of MLPA data analysis are improved.

Disclosed herein are systems for modifying nucleic acid splicing of a target RNA, e.g. SCN1A mRNA. The systems can be used in methods, e.g., methods of treating a genetic disorder, e.g., epilepsy. The systems can include an expression system or a modified small nuclear RNA (snRNA) that includes an exon splicing silencer (ESS) sequence and an antisense nucleic acid sequence that targets a target RNA.

The present disclosure relates to compositions and methods for treating genetic disorders caused by nonsense mutations using anticodon-engineered transfer RNA (ACE-tRNA) constructs. These DNA-based ACE-tRNA constructs are designed to suppress premature termination codons (PTCs) and restore the expression of full-length, functional proteins. The disclosure further provides formulations of ACE-tRNA constructs with poly(amine-co-ester) (PACE) polymeric nanoparticles to improve stability, protect nucleic acids, and enhance delivery to airway epithelial cells. Also described are functionalized ACE-tRNA Picovectors (sLPVs) incorporating targeting elements such as nuclear localization signals (NLSs), nucleolar localization sequences (NoLSs), and DNA nuclear targeting sequences (DTSs) to improve nuclear import and localization.

Described herein are systems and methods and systems for preimplantation genetic testing of an embryo derived from consanguineous parents (PGT-C). The methods involve receiving embryonic genetic data and determining a proportion of the genome in long runs of homozygosity for the entire genome (global F value) as well as for one or more regions of interest within the genome (localized F values). The localized F values are weighted based on one or more factors relating to genetic viability and genetic disorders of the embryo. The global F value and weighted localized F values may be integrated with other genetic data to predict relevant risk scores.

Chronic nephropathies, in particular tubulointertial nephropathy or tubulointertial nephropathy with fibrosis feature represent a real global public health concern. In particular, nephronophthisis (NPH) is an orphan genetic disease affecting the kidney. This recessive affection usually manifests with polyuria followed by a gradual reduction in kidney function related to progressive renal scarring. To date, no treatment is available for this affection. Now the inventors show that inhibition of the Hippo signalling pathway represents a new therapeutic avenue for the treatment of chronic nephropathies such as NPH. In particular, the inventors show that inhibition of MST1 / 2 or LATS1 / 2 reduces the NPH pro-inflammatory signature in mIMCD-3 renal cells even in response to uropathogenic bacteria. Thus the present invention relates to use of inhibitors of the Hippo signalling pathway for the treatment of chronic nephropathies.

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 invention relates to the field of pathologies affecting the central nervous system, particularly severe cerebral pathologies, especially those restricted by the presence of the blood-brain barrier (BBB): gliomas, brain 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 (thrombosis) 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, its use, and intermediate polymer or copolymer compounds. Abbreviated figure: 0

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 present invention is related to a composition comprising a novel chemical compound with the chemical Name "4-(4-((4-Aminobutan-2yl)oxy)-2,6-dibromophenoxy)-2- isopropylphenol" and its use. The 4-(4-((4-Aminobutan-2yl)oxy)-2,6-dibromophenoxy)-2- isopropylphenol and related compounds are useful for treating microgravity induced damage such as skeletal muscle atrophy and dysfunction as well as cardiac dysfunction and are also useful for human diseases and conditions accompanied by significant loss of muscle mass and reduced endurance capacity, such as immobilized patients, cancer, heart failure, sepsis, diabetes mellitus, muscle genetic diseases and neurodegenerative disorders. In addition, 4-(4-((4- Aminobutan-2yl)oxy)-2,6-dibromophenoxy)-2-isopropylphenol and related compounds are useful for treating human diseases related to muscle degeneration and ageing such as sarcopenia and heart failure.

Described herein are systems and methods and systems for preimplantation genetic testing of an embryo derived from consanguineous parents (PGT-C). The methods involve receiving embryonic genetic data and determining a proportion of the genome in long runs of homozygosity for the entire genome (global F value) as well as for one or more regions of interest within the genome (localized F values). The localized F values are weighted based on one or more factors relating to genetic viability and genetic disorders of the embryo. The global F value and weighted localized F values may be integrated with other genetic data to predict relevant risk scores.

The present invention relates to a combination comprising two or more mRNA molecules, or a single mRNA molecule encoding a first molecule which is a therapeutic or immunogenic protein or peptide and a second molecule which is a protein or peptide having the ability to modulate an immune response to the first molecule and / or the translation product of the first molecule, wherein the combination comprises at least one first mRNA molecule encoding a first molecule which is a therapeutic or immunogenic protein or peptide, and at least one second mRNA molecule encoding a second molecule which is a protein or peptide having the ability to modulate an immune response to the first molecule and / or the translation product of the first molecule. The present invention also relates to a host cell comprising the combination or single mRNA molecule described in the present invention, a pharmaceutical composition comprising the combination, the single mRNA molecule, or the host cell of the present invention, and a vaccine comprising the combination, the single mRNA molecule, the host cell, or the pharmaceutical composition described in the present invention. Furthermore, kits comprising the combination, the single mRNA molecule, the host cell, the pharmaceutical composition, or the vaccine described in the present invention are provided. The present invention also relates to the combination, the single mRNA molecule, the host cell, the pharmaceutical composition, the vaccine, or the kit described in the present invention for use in pharmaceuticals. Finally, the present invention also relates to the combination, the single mRNA molecule, the host cell, the pharmaceutical composition, the vaccine, or the kit described in the present invention for use in methods for the prevention and / or treatment of infectious, hereditary, or proliferative diseases.