153 results about "Inherited disease" 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 relates to the technical field of stem cells, in particular to a lentivirus envelope plasmid combination and application thereof, a lentivirus and a packaging method thereof and a method for transduction of hematopoietic stem cells. The invention provides an envelope plasmid combination for lentivirus packaging, which is composed of lentivirus packaging plasmids containing VSVG glycoprotein and lentivirus packaging plasmids containing BaEV glycoprotein in a ratio of 3: 7. The invention further provides a method for transduction of the hematopoietic stem cells by the lentivirus, the method is simple and convenient to operate, the long-term dryness of the hematopoietic stem cells in vitro can be maintained, efficient and stable transduction of the hematopoietic stem cells can be realized, and the transduction rate is greater than 90%. The lentivirus transduction method hematopoietic stem cells can be used for hematopoietic stem cell gene therapy hematopoietic system genetic diseases, such as severe combined immunodeficiency, beta-thalassemia and sickle cell disease, Wiskott-Aldrich syndrome and the like, and the application prospect is good.

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.

Provided herein are Cas endonucleases (and functional fragments, functional variants, and domains thereof), nucleic acid molecules encoding the same, and systems comprising the same. The disclosure further relates to methods of utilizing the Cas endonucleases (or nucleic acid molecules encoding the same), including, e.g., in methods of editing a nucleic acid molecule (e.g., a gene) and methods of treating diseases (e.g., genetic diseases).

The present disclosure relates generally to methods for improving the preparation of spatial transcriptomic RNA libraries, such as mRNA libraries, by improving in situ capture of RNA transcript information from tissue samples. The spatial transcriptomic library from a tissue sample can be used to determine genetic maps and help diagnose persons having or at risk of having diseases, such as cancer, genetic diseases, autoimmune diseases, and other indications, and improve treatment of subjects.

The invention relates to the field of bioengineering, in particular to a bilateral cleft lip mouse model based on Pitx2-Cre conditional knockout of Bmp4 as well as a construction method and application of the bilateral cleft lip mouse model. The invention aims to construct a stable bilateral cleft lip mouse model. Experiments find that the Bmp4 gene is expressed in the epithelium of the frontal nose process and the maxillary process at the early lip stage in E9.25. The spatio-temporal expression mode of the Pitx2 gene in the early primordium epithelium is highly consistent with the spatio-temporal expression mode of the Bmp4 gene. Based on this, the inventor constructs a Bmp4 gene knockout model driven by an endogenous Pitx2 gene promoter, and finds that the mouse model shows a 100% bilateral cleft lip phenotype. Compared with the reported Netin-Cre, the Nestin-Cre has the advantages that the Nestin The bilateral cleft lip model constructed by the method is more stable, can better represent genetic diseases of human cleft lip, and has important research significance.

The invention relates to a nanoparticle system for small intestine delivery, which is used for delivering exogenous miR-122-5p to the intestinal tract and comprises a miRNA-protamine compound inner core, a liposome middle layer wrapping the inner core and a p123 functional shell wrapping the liposome. Due to the adoption of the technical scheme, a nano-targeting delivery technology is combined with paternal epigenetic programming intervention for the first time, and a brand-new nano-drug treatment thought is provided for intergenerational genetic diseases caused by exposure of environmental adverse factors. By delivering exogenous miR-122-5p to the intestinal tract, the miRNA spectrum unbalanced due to exposure of paternal BaP can be directly improved.

The present invention relates to engineered liver-specific core promoters, synthetic promoters (which contains the engineered core promoters and enhancers), expression vectors (which contains the synthetic promoter), as well as methods of using the promoter or the expression vector thereof to address the need in the field, including treatment of various genetic diseases or conditions associated with the liver. In some embodiments, the liver-specific promoter includes continuous or discontinuous genome sequences from SERPINA1 genome.

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 invention discloses a laying hen genetic disease knowledge graph construction and intelligent decision support system. The system comprises a genetic disease weak supervision graph extraction module, a disease multi-factor diagnosis module, a group health risk clustering module, a multi-omics graph analysis module, a genetic disease knowledge graph construction module and an intelligent decision support module. According to the system, laying hen genes, physiological indexes, breeding environments and multi-omics data are collected through gene sequencing and the like, a gene disease association graph is generated through weak supervision graph extraction, a disease diagnosis result is generated through multi-factor diagnosis, health risk grades are divided through risk clustering, and an association graph is generated through multi-omics analysis; and a genetic disease knowledge graph is constructed, and an intelligent decision scheme is generated in combination with real-time data and an algorithm. The system improves the accuracy of laying hen genetic disease prevention and control and the intelligent level of breeding management, guarantees the economic benefits of breeding, and is suitable for large-scale breeding scenes of laying hens.

The proposed method utilizes telomere length as a marker for estimating the proportion of different components present in a DNA mixture with broad applications in genetic testing. It can be used as an independent or complementary technique to existing methods to increase the precision and reliability of results. In the context of non-invasive prenatal testing (NIRT), the method can provide valuable information about the proportion of fetal DNA present in a maternal blood sample, allowing for the accurate identification of genetic disorders and abnormalities. The method is also applicable in the detection and characterization of ongoing oncological disease, where anomalies in telomere length can indicate the presence of tumor DNA fragments in blood plasma samples.

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.

Compositions and methods for detecting structural variations (SVs) in target genes or for genetic mapping of movable transposable elements are disclosed, the target genes relating to disease pathologies commonly found in large Mendelian genomics projects, and the movable transposable elements relating to genetic diseases, cancer, and aging. The method comprises: (i) contacting a sample containing genomic DNA with a DNA endonuclease for an effective amount of time to cleave the genomic DNA into fragments, the genomic DNA being uncrosslinked; (ii) subjecting the fragments obtained from step (b) to a DNA ligase to obtain circularized DNA; (iii) subjecting the circularized DNA to reverse PCR amplification containing a reverse primer, wherein the reverse primer is designed to match a expected wild-type sequence near a suspected mutant locus in the gene; and (iv) sequencing the amplified products. Exemplary conditions include Bardet-Biedel syndrome; severe upper and lower limb defects; retinitis pigmentosa; syndromic microcephaly; spastic paraplegia; and atypical hemolytic uremic syndrome.

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

Myotonic Dystrophy type 1 (DM1) is an inherited disease characterized by multi-systemic symptoms, particularly in skeletal muscles (progressive weakness and atrophy, myotonia). The inventors screened 7 500 bioactive compounds for their ability to improve the myogenic fusion and reduce the molecular hallmarks of DM1 skeletal muscle cells. The inventors found that five compounds, all inhibiting HDAC6, a cytoplasmic histone deacetylase, were effective at the micromolar range in normalizing the myogenic fusion, reducing the number of nuclear foci of mutant DMPK mRNA, decreasing the expression level of DMPK mRNA, restoring the splicing of several genes, and increasing the acetylation of SMAD3, a transcription factor involved in muscle development. The effects of HDAC6 inhibitors were observed both in immortalized and hiPSC-derived skeletal muscle cells from DM1 patients, and in different stages of differentiation. Thus, the present invention relates to the use of selective HDAC6 inhibitors for the treatment of DM1.

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 invention relates to the technical field of data mining, and discloses an SNP site mining method and system based on Transform model ensemble learning, and the method comprises the steps: obtaining genetic data containing chromosome SNP sites, and carrying out the screening processing of the genetic data; dividing the screened genetic data into a training set, a verification set and a test set; using the training set and the verification set to construct a basic classifier based on a Transform model; analyzing the basic classifier to obtain a remarkable SNP (Single Nucleotide Polymorphism) site; carrying out integrated learning on the basic classifier by utilizing the test set, and constructing and screening out an optimal element classifier; and carrying out classification processing on the significant SNP sites by utilizing the optimal meta classifier, and screening out the significant SNP sites related to the genetic diseases. According to the method, the basic classifier is constructed by using the Transform model, the optimal element classifier is constructed through analysis and ensemble learning, and the feature information is integrated, so that the significant SNP loci related to the genetic diseases are finally obtained, and the mining efficiency and accuracy of the SNP loci are improved.

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.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. Applicants engineered an AAV capsid, BI-hTFRl, that binds human Transferrin Receptor (TfRl), a protein expressed on the blood-brain barrier (BBB). BI-hTFRl was actively transported across a human brain endothelial cell layer and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFRl substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9.

The application discloses a kind of neurogenetic disease identification model construction method and system, it is related to neurogenetic disease identification technical field.The method includes: obtaining multiple identification results and multiple user feature sets of neurogenetic disease identification, and multiple inter-class difference degrees are obtained by analysis;Based on multiple identification results and multiple user feature sets, train first identification model;According to multiple inter-class difference degrees, configure user feature synthesis strategy, generate synthetic user feature set and synthetic identification result, carry out the reinforcement learning of first identification model, obtain second identification model;Test the combined identification error rate of second identification model, combined with multiple inter-class difference degrees again configure synthetic strategy, continue to generate synthetic user feature set and synthetic identification result, carry out reinforcement learning, obtain third identification model.The application solves the problem that neurogenetic disease identification model is poor in generalization performance, easily confused class and low in recognition accuracy under small sample condition.

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 disclosure provides, in various embodiments, compositions, such as polypeptides, polynucleotides, gene editing system, small molecules, vectors or host cells, that comprises and / or modulate expression or activity of immune regulation-associated proteins. The disclosure also provides, in various embodiments, methods of treating aging, senescence, fibrosis, a metabolic disease, cardiovascular disease, an endocrine-associated disorder, a genetic disease, cancer, an infection, an immunological disease, an indication treated with hormone, growth factor and / or protein replacement, or a combination thereof using an agent that comprises and / or modulates expression or activity of an immune regulation-associated protein and methods of identifying said agent.

Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1(NF1) protein (e.g., mini-NF1 protein and / or full-length NF1 protein) to target cell (e.g., cells and / or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and / or full-length NF1 protein) or variants thereof.

The invention relates to a nucleic acid molecule complex for pseudouridylation of a target RNA in a mammalian cell comprising a guide RNA (gRNA) that at one end is flanked by a first twister ribozyme and at its other end by a second twister ribozyme to generate a circular gRNA, wherein the nucleic acid molecule complex has the capability to generate circular gRNA which is characterized by a secondary structure comprising two pseudouridylation pockets that harbor antisense guide sequences. More specifically, the first twister ribozyme is a P3 twister ribozyme and the second twister ribozyme is a P1 twister ribozyme, wherein each twister ribozyme is separated from the gRNA by a linker. In a further aspect, the invention relates to a method for generating circular gRNA. The invention furthermore relates to a nucleic acid molecule complex as defined herein for use in the treatment of a genetic disease caused by a premature stop codon. It furthermore relates to a pharmaceutical composition, and a delivery vector to express the construct in mammalian cells to generate circular gRNA.

Compositions and methods relating to a pharmacological therapy for a human genetic disease, specifically mitochondrial DNA depletion-deletions syndromes, and more specifically, those related to mutations in the GUK1 gene. The pharmacological therapy involves the administration of deoxyguanosine (dG), a purine nucleoside phosphorylase (PNP) inhibitor, including but not limited to forodesine, or both.

The present disclosure provides one or more amino lipids such as an amino lipids containing a sulfonic acid or sulfonic acid derivative of the formulas:wherein the variables are as defined herein. These amino lipids may be used in compositions with one or more helper lipids and a nucleic acid therapeutic agent. These compositions may be used to treat a disease or disorder such as cancer, cystic fibrosis, or other genetic diseases.

Disclosed are split complementary base editing systems based on bimolecular deaminases and uses thereof. A split complementary base editing system mainly includes base editing fusion proteins A and B that are from splitting at a deaminase domain embedded inside a Cas9 nickase (nCas9), and a guide RNA (gRNA). The present disclosures of split complementary cytosine base editing systems can greatly reduce Cas9-dependent and Cas9-independent off-target effects in the genome while maintaining robust on-target cytosine base editing. The present disclosures also provide the split complementary adenine base editing systems. The split complementary cytosine (adenine) base editing systems are widely applicable to various eukaryotic organisms, and can be used in crop genetic breeding, animal breed improvement, and even clinical treatment of human genetic diseases.

The present invention relates to a multiplex Sanger sequencing kit and method. Using the kit and method according to the present invention can facilitate multiple amplification and sequencing in Sanger sequencing for diagnosing genetic diseases and the like, and thus can significantly save costs and time.