12 results about "SMN1" patented technology

The present invention refers to a composition comprising an inhibitory molecule capable of inhibiting the expression of a gene selected from any of the list consisting of SMPD1, ARAP1, CST3, GSN, HDAC5, PACS1, TOM1L2, TSC22D3 and USP20 or homologues thereof and increasing the levels of endogenous SMN1 and / or SMN2 proteins, or a mixture of two or more of said molecules, for use in the treatment of Spinal Muscular Atrophy (SMA) in a subject in need thereof.

Disclosed is a method of determining whether a human subject is not a carrier of spinal muscular atrophy (SMA). This method includes the steps of (i) collecting a genomic deoxyribonucleic acid (DNA) sample from a human subject; (ii) screening the genomic DNA sample to determine the human subject's copy number of survival of motor neuron 1 (SMN1) gene and whether one of the copies of the SMN1 gene is positive for a polymorphism associated with non-carriers of SMA having two copies of the SMN1 gene; and (iii) determining the human subject as not a carrier of SMA if the human subject includes two copies of the SMN1 gene with one of those copies being positive for the polymorphism. Also disclosed is a method of determining whether an individual has a decreased risk of being a carrier of spinal muscular atrophy (SMA), where the individual is identified to have a decreased risk of being a carrier of SMA when the individual has two copies of the SMN1 gene with one of those copies being positive for the polymorphism.

To provide a combination therapy for spinal muscular atrophy.SOLUTION: Aspects of the present application relate to compositions and methods for treating spinal muscular atrophy in a subject. In particular, this application provides therapeutically combinations of recombinant nucleic acids encoding Survival of Motor Neuron 1 (SMN1) proteins (e.g., in viral vectors) and antisense oligonucleotides (ASOs) that increase full-length Survival of Motor Neuron 2 (SMN2) mRNA (e.g., ASOs that target nucleic acids molecules encoding Survival of Motor Neuron 2 (SMN2) and promote inclusion of exon 7 in SMN2mRNA).SELECTED DRAWING: None

This application discloses a primer set and its design method for detecting copy number variations in the SMN1 and SMN2 genes. The primer set includes a first primer for detecting exon 7 of the SMN1 gene, a second primer for detecting exon 8 of the SMN1 gene, a third primer for detecting exon 7 of the SMN2 gene, and a fourth primer for detecting exon 8 of the SMN2 gene. The 3′ ends of each of the first to fourth primers independently meet the following conditions: A1) The first base is absolutely conserved and is specifically complementary to the sequences of exons 7, 8, 7, and 8 of the SMN1, SMN1, and SMN2 genes, respectively; and A2) At least one mismatched base is introduced at positions 2 to 4. Using this primer set to detect copy number variations in the SMN1 and SMN2 genes ensures both specificity and amplification efficiency, as well as minimal dosage.

The application discloses application of a gene editing system in preparation of a spinal muscular atrophy model pig nuclear transfer donor cell with SMN1 gene mutation. The application provides application of SMN1-gRNA3 shown in SEQ ID NO: 16, SMN1-gRNA4 shown in SEQ ID NO: 17 and NCN protein in preparation of a kit. The application also provides a method for preparing a recombinant pig cell: SMN1-gRNA3, SMN1-gRNA4 and NCN protein are co-transfected into a pig cell to obtain a recombinant pig cell. The recombinant pig cell is a recombinant pig cell with SMN1 gene mutation. The kit is used for: preparing a recombinant pig cell; preparing a spinal muscular atrophy model pig; preparing a spinal muscular atrophy cell model or a spinal muscular atrophy tissue model or a spinal muscular atrophy organ model. The application has great application value for research and development of spinal muscular atrophy drugs and revealing the pathogenesis of the disease.

Aspects of the disclosure relate to compositions and methods for delivery of certain gene products (e.g., proteins, nucleic acids, etc.) to a subject, e.g., to the central nervous system (CNS) of a subject. The disclosure is based, in part, on expression cassettes (e.g., isolated nucleic acids) comprising a nucleic acid sequence operably linked to a human SMN1 promoter or a variant of a human SMN1 promoter, for example variants that are truncated relative to native SMN1 promoters.

The present invention discloses a method for detecting the human survival motor neuron gene (SMN), a kit for detecting the human survival motor neuron gene (SMN), a method for calculating the copy number variation of the human survival motor neuron gene (SMN), and the application of the calculation method for accurately and quantitatively detecting high copy numbers of the human survival motor neuron gene (SMN). The method of the present invention enables simultaneous detection of copy number variations of SMN1 exon 7 and exon 8 and SMN2 exon 7 and exon 8, SMN1 minor mutations, compound heterozygous mutations, and silent carriers in a single tube.

Provided herein are methods and compositions for the detection of silent carriers of chromosomal deletion alleles in a human subject using haploid cells (e.g., sperm cells or egg cells) derived from the subject. The methods provided herein allow for the detection of silent (2+0) carriers of SMA, where the individual has a deletion of the SMN1 gene on one chromosome 5 homolog and two or more copies of the SMN1 gene on the other chromosome 5 homolog.

To provide a method for simultaneously measuring amounts of TREC, KREC and SMN1, an inspection method using the same, and a kit thereof.SOLUTION: A method for simultaneously measuring amounts of T-cell receptor recombination excision circle (TREC), Igκ-deleting recombination excision circle (KREC) and SMN1 gene by quantitative PCR includes: (i) a process of mixing DNA and PCR reagent collected from a subject, where the PCR reagent includes a set of primers and a set of probes; and (ii) a process of performing quantitative PCR reaction to quantitatively determine the amounts of TREC, KREC and SMN1 gene, where the set of primers includes six primers including base sequences shown by sequence numbers 4, 5, 7, 10, 37 and 38, and the set of probes includes three probes including base sequences shown by sequence numbers 22, 23 and 28.SELECTED DRAWING: None

To provide a combination therapy for spinal muscular atrophy.SOLUTION: Aspects of the application relate to compositions and methods for treating spinal muscular atrophy in a subject. In particular, this application provides therapeutic combinations of a small molecule that promotes SMN function and / or a recombinant nucleic acid that encodes the survival of motor neuron 1 (SMN1) protein (e.g., in a viral vector), and / or an antisense oligonucleotide (ASO) that increases full-length survival of motor neuron 2 (SMN2) mRNA (e.g., that is targeted to a nucleic acid molecule encoding the survival of motor neuron 2 (SMN2) and promotes the inclusion of exon 7 in SMN2 mRNA).SELECTED DRAWING: None

The invention relates to a CRISPR-Cas (clustered regularly interspaced short palindromic repeats-associated proteins) system, in particular to crRNA and application thereof. The crRNA is ribonucleic acid as shown in SEQ ID NO.14 or crRNA having two different basic groups with ribonucleic acid containing the sequence as shown in SEQ ID NO.14, the position of one different basic group is the fifth basic group at the 5 end of the sequence as shown in SEQ ID NO.14, and the position of the other different basic group is the second, sixth, tenth, eleventh, twelfth, thirteenth, fifteenth or nineteenth position at the 5 end of the sequence as shown in SEQ ID NO.14. The one-step method based on combination of crRNA containing two different basic groups and isothermal amplification can be used for specifically detecting the mutation condition of the SMN1 gene, amplification and detection are combined into one tube, and detection can be completed within half an hour, so that whether a detected person suffers from spinal muscular atrophy or not is judged.

The application provides a primer probe and kit for detecting SMN1 gene mutation. The kit comprises primers for detecting deletion mutation of SMN1 gene exons 7 and 8 respectively, and corresponding mutation detection probes and blocking probes. The application is more accurate and reliable by reducing the interference of SMN2 pseudogene. The triple amplification of SMN1 gene exons 7 and 8 and the reference Actin gene is completed in a single reaction tube by using the principle of multiplex PCR amplification, thereby improving the efficiency. Through reaction system optimization, the micro blood sample can be used for PCR amplification without purification of genomic DNA, the pretreatment is completed in 15 minutes, the whole detection is completed in about 2.5 hours, time and purification cost are saved, and the kit is suitable for high-throughput screening and detection of neonatal dried blood spots.