44 results about "Mutant allele" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The present disclosure provides compositions and methods for altering auxin accumulation in corn or maize plants. Methods and compositions are also provided for altering the expression of genes related to auxin efflux through editing or mutagenesis of a brachytic2 (br2) gene to introduce a premature stop codon or a deletion into the gene such that a truncated Br2 protein encoded by the mutant allele of the br2 gene, which may be a dominant or semi-dominant allele, has at least part of a transmembrane domain without a nucleotide binding domain or motif. Modified plant, plant parts and cells having such a mutant allele with reduced or altered expression or activity of a br2 gene product can have improved characteristics, such as reduced plant height and increased lodging resistance, but without off-types in the plant.

The disclosure relates to soybean genes and mutant alleles thereof associated with improved flavor characteristics. Also disclosed are soybean plants comprising combinations of the mutant alleles along with related methods of improving one or more flavor characteristics of soybean seed.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention discloses a rice photo-thermo-sensitive male sterility mutant Osgpat6.1, a corresponding gene locus OsGPAT6.1 of the rice photo-thermo-sensitive male sterility mutant Osgpat6.1 and application of a coding protein of the rice photo-thermo-sensitive male sterility mutant The phenotypic gene OsGPAT6.1 for controlling the photo-thermo-sensitive male sterility of the rice is obtained by cloning through phenotypic analysis of a mutant and preliminary positioning of a target gene, an amino acid sequence of the phenotypic gene OsGPAT6.1 is encoded as shown in SEQ ID NO.1 to form a protein, and the gene affects the development process of rice pollen by affecting tapetum degradation. The OsGPAT6.1 gene is subjected to gene editing, or a mutant allele of the OsGPAT6.1 gene is introduced into a conventional rice variety in a hybridization manner, so that a photo-thermo-sensitive male sterile material for a two-line sterile line can be obtained. The gene and the encoding protein thereof can be applied to creation of photo-thermo-sensitive sterile rice and germplasm genetic improvement of the photo-thermo-sensitive sterile rice.

The invention relates to a mutant calreticulin for diagnosis of myeloid malignant tumors. A method for diagnosing myeloid malignancies comprising determining the presence of a mutant allele of a calreticulin gene is disclosed. In addition, genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are also subject matter of the invention. Furthermore, the invention relates to the medical use of inhibitors of the mutant calreticulin.

Provided herein are highly transformable maize plants, referred to as HI-NA plants, and methods of their production and use. A HI-NA plant, as disclosed herein, is homozygous for a loss-of-function mutant allele in the patatin-like phospholipase A2α (MATL) gene and at least heterozygous for one or more QTL and / or gene alleles that are responsible for increased haploid induction and / or transformation frequency in plants. A HI-NA plant, as disclosed herein, may also have a cytotype A background, which may render it highly transformable. Also provided are methods of producing I-NA plants and methods of using a HI-NA plant for editing plant genomic DNA.

The invention provides application of combination of an mTOR inhibitor and an EPAS1 inhibitor in preparation of a medicine for treating myeloproliferative tumors, through combined use of the mTOR inhibitor everolimus and the EPAS1 inhibitor PT2385, JAK2V617F mutation-driven metabolic disorder is targeted, metabolic reprogramming is effectively reversed (the lactic acid level is reduced, the alpha-ketoglutaric acid level is increased, and the lactic acid / alpha-KG ratio is corrected), and the treatment effect on myeloproliferative tumors is improved. The JAK inhibitor can be used for treating MPN, synergistically relieving splenomegaly, reversing myelofibrosis and reducing mutation allele load, the curative effect is remarkably superior to that of existing JAK inhibitor single-drug treatment, and an innovative scheme with disease modification potential is provided for MPN.

Methods and compositions for detecting genetic instability using digital amplification assays. The methods may be performed in a set of isolated volumes and generally may involve competitive hybridization of a competitor and a probe / primer with a normal allele and one or more mutant alleles of a microsatellite locus. The competitor may be configured to compete similarly with, or to outcompete, the primer / probe for hybridization with the normal allele. The primer / probe may be configured to outcompete the competitor for hybridization with various mutant alleles of the locus that alter the length of the repetitive sequence by different amounts. Isolated volumes in which the primer / probe outcompetes the competitor may be enumerated, and represent one or more of the mutant alleles. The methods may enable diagnosing microsatellite instability and treating a subject based on the diagnosis.

The invention discloses a method for detecting KCNJ8 gene c.263Cgt; according to the technical scheme provided by the invention, the prevention and treatment efficiency of the hereditary arrhythmia is remarkably improved on the clinical diagnosis and treatment level. KCNJ8-A88G mutation detection is completed within 45 minutes through the ARMS-PCR technology, the mutation allele frequency as low as 0.1% can be accurately recognized through the sensitivity of 99.8%, and the diagnosis period is greatly shortened compared with traditional sequencing. On the treatment level, the KATP channel inhibitor is screened, and arrhythmia after myocardial infarction can be effectively prevented. According to the established'genotype-phenotype-treatment response 'correlation model, not only is the prevention and treatment level of diseases such as the J-wave syndrome improved, but also a conversion benchmark from laboratory basic research to clinical application is established.

An oligonucleotide probe for detecting a genomic alteration includes a first complementary region, a second complementary region, and a semi-complementary region. The first complementary region includes at least three nucleotides that are completely complementary to a mutant allele of a portion of a genomic sequence, the includes at least three nucleotides that are completely complementary to the mutant allele and to the wild type allele, and the semi-complementary region is adjacently flanked by the first complementary region and the second complementary region. The nucleotides of the semi-complementary region are completely complementary to the mutant allele and are not completely complementary to the wild type allele, the first complementary region comprises a first locked nucleic acid adjacent to the semi-complementary region, the second complementary region comprises a second locked nucleic acid adjacent to the semi-complementary region, and the semi-complementary region comprises a third locked nucleic acid.

To provide a method for efficiently and accurately distinguishing two similar diseases that differ in the presence or absence of a mutant allele in the same gene region.SOLUTION: A method for distinguishing between a genetic disease caused by a codon mutation in a gene and another disease includes the steps of: performing an amplification reaction to amplify a genetic region containing the codon, the amplification reaction including adding a DNA primer for amplifying the genetic region containing the codon and a PNA that inhibits the amplification of a normal allele containing the codon; and treating a product obtained by the amplification reaction with a restriction enzyme that specifically recognizes and cleaves either a base sequence containing the codon with the mutation or a base sequence containing the codon without the mutation, thereby obtaining a restriction enzyme-treated product.SELECTED DRAWING: Figure 3

The invention discloses a kit for detecting circulating tumor DNA (deoxyribonucleic acid) of portal vein and branch vein blood of portal vein. The kit comprises: a nucleic acid extraction assembly comprising an optimized lysate and selectively bound magnetic beads; the library construction component comprises a terminal repair / tailing fusion enzyme and a Y-shaped linker with a molecular identifier; the targeted enrichment assembly comprises a specific primer group and a probe group and is used for enriching related gene targets of the abdominal organ tumors; and necessary reaction components. Through an optimized nucleic acid extraction method, an efficient library construction system and a precise targeted enrichment technology, high-sensitivity detection of low-abundance ctDNA in portal venous blood is achieved, and the lower detection limit reaches 0.1% of mutation allele frequency. The kit is particularly suitable for early diagnosis, curative effect monitoring and prognosis evaluation of abdominal organ tumors such as intestinal cancer, liver cancer and pancreatic cancer.

An agent for treating a common form of autosomal dominant retinitis pigmentosa (ADRP) is disclosed, wherein the agent comprises a first nucleotide sequence encoding a CRISPR-associated (Cas) endonuclease which binds to an NG or NNGRRT PAM (protospacer adjacent motif) sequence, and a second nucleotide sequence encoding or comprising a guide RNA (gRNA) capable of forming a CRISPR-Cas complex with said Cas endonuclease, wherein the gRNA is specifically targeted to a target mutant allele selected from RHOP23H and NR2E3G56R.

The invention discloses an NtPPO gene heterozygous mutant and application thereof. The application comprises the following steps: (1) reducing polyphenol oxidase activity of tobacco leaves; (2) the browning degree of the flue-cured tobacco during baking is reduced; the NtPPO gene mutant comprises mutant types of NtPPO1, NtPPO2, NtPPO3, NtPPO4, NtPPO9, NtPPO10, NtPPO11, NtPPO12 and NtPPO13, and the mutant types of the NtPPO4 are limited as follows: a mutant allele NtPPO4-1 positioned on a first chromosome and a second chromosome and a mutant allele NtPPO4-2 positioned on a third chromosome and a fourth chromosome; the mutant type of the NtPPO9 is limited as follows: a mutant allele NtPPO9-1 positioned on a first chromosome and a second chromosome, and a mutant allele NtPPO9-2 positioned on a third chromosome and a fourth chromosome; the mutant type of the NtPPO10 is limited as follows: a mutant allele NtPPO10-1 positioned on a first chromosome and a second chromosome, and a mutant allele NtPPO10-2 positioned on a third chromosome and a fourth chromosome.

The application provides a circulating tumor DNA-based mutant gene detection method and application thereof, and relates to the technical field of biological detection.The application provides a circulating tumor DNA-based mutant gene detection method, adopts a customized panel technical route, adopts a single-stranded library construction method, preliminarily amplifies free DNA, and then performs target enrichment based on UMI multiplex PCR, so that the detection sensitivity and specificity are effectively improved.It is proved through tests that the method can simultaneously analyze multiple gene mutation results of the same patient, has a sensitivity of more than 70% and a specificity of more than 90% on the mutation allele ratio (AF), and has a good application prospect for MRD monitoring.

Methods for inactivating in a cell a mutant allele of the elastase, neutrophil expressed gene (ELANE gene) gene having a mutation associated with severe congenital neutropenia (SCN) or cyclic neutropenia (CyN) and which cell is heterozygous at one or more polymorphic sites selected from the group consisting of: rs10424470, rs4807932, rs10414837, rs376107533, rs3761010, rs10413889, rs3761007, rs10409474, rs3761005, rs351107, rs3761001, rs740021, rs781452480, rs371057361, rs570466264, rs1041904080, rs7250194, rs17216649, rs199720952, rs6510983, rs17223066, rs7255385, rs112639467, rs141213775, rs28591229, rs10469327, rs3834645, rs1683564, rs71335276, and rs8107095, the method comprisingintroducing to the cell a composition comprising:a CRISPR nuclease or a sequence encoding the CRISPR nuclease; anda first RNA molecule comprising a guide sequence portion having 17-30 nucleotides,wherein a complex of the CRISPR nuclease and the first RNA molecule affects a double strand break in the mutant allele of the ELANE genethe method optionally further comprising introduction of a second RNA molecule comprising a guide sequence portion capable of complexing with a CRISPR nuclease, wherein the complex of the second RNA molecule and CRISPR nuclease affects a second double strand break in the ELANE gene.

This invention relates to adjustable carrying capacity COL6A1 The invention relates to an oligonucleotide expressing a dominant mutant allele, wherein the downregulation is achieved by hybridization of the oligonucleotide with the RNA transcript of the allele at the dominant mutation site, and the oligonucleotide does not inhibit the expression of the wild-type allele, or downregulates the expression of the wild-type allele to a lesser extent than it downregulates the expression of the allele carrying the dominant mutant. The invention also relates to the use of compositions to treat patients with muscular dystrophy, particularly those with malnutrition related to type VI collagen.

The present invention relates to a melon plant, wherein said plant comprises in its genome homozygously a mutant allele of the stay-green (sgr) gene on chromosome 9, wherein said mutant allele of the sgr gene comprises at least one loss-of-function mutation compared to the sequence of the wild type sgr allele (SEQ ID NO: 1), and wherein said mutant allele of the sgr gene confers fruit skin color stability at ripening and / or during the post-harvest period of the fruit of said plant compared to an isogenic non-long shelf life (non-LSL) melon plant not comprising said mutant allele. The present invention also relates to parts, cells and seeds of said plant, as well as related methods and processes.

Aspects of the present disclosure relate to conjugates, and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such conjugates (e.g., each conjugate represented by the exemplary formula below) comprising a phosphorodiamidate morpholino oligomer (e.g., useful for targeting DMD) covalently linked to an antibody (e.g., an anti-TfR1 antibody). Also provided is the use of these formulations for treating subjects with a mutated DMD allele associated with Duchenne muscular dystrophy. JPEG2026503873000028.jpg63163

A pharmaceutical composition useful for the treatment of a cancer characterized by the presence of a mutant allele of IDH1 / 2 is provided, comprising a compound of the following formula:

The invention provides an SNP molecular marker related to meat pigeon unsaturated fatty acid EPA and application of the SNP molecular marker, and belongs to the technical field of molecular markers. The invention discloses an SNP (Single Nucleotide Polymorphism) molecular marker related to meat pigeon unsaturated fatty acid EPA (Eicosapentaenoic Acid), the SNP molecular marker is located at the 101st site on a DNA (Deoxyribonucleic Acid) fragment as shown in SEQ ID No.1, and a mutant gene is G or A. Through genotyping of a population level and determination of the content of muscle EPA, it is found that SNP mutation is significantly related to the content of EPA in meat pigeon muscles, and the muscle EPA level of a carrier of a mutant allele (A / A) is generally higher than that of a wild allele individual. The invention shows that the site can be used as a functional molecular marker closely related to the nutritional traits of the EPA of the pigeon meat, and has potential molecular breeding value.

The invention relates to a magnetic bead, a kit and a method for extracting short-fragment DNA (deoxyribonucleic acid). The magnetic beads are prepared by the following method: (1) taking magnetic beads, and adding a water-soluble carbodiimide activator and an activation synergist for activation; (2) taking the activated magnetic beads, and adding polyethyleneimine for reaction to obtain polyethyleneimine modified magnetic beads; and (3) taking the polyethyleneimine modified magnetic beads, adding poly N-isopropylacrylamide, the water-soluble carbodiimide activator and the activation synergist, and carrying out a reaction so as to obtain the magnetic beads. The surface of the magnetic bead is coated with a double-layer functional polymer to construct double channels, traditional chemical competition is replaced with physical screening, the enrichment efficiency and selectivity of short-fragment DNA with the average length of 166 bp are remarkably improved, and the magnetic bead is very suitable for cffDNA capture. By using the magnetic bead and the method, the usage amount of maternal plasma can be effectively reduced, the fetal fraction is increased, and the detection limit of mutant alleles is reduced.

The present invention is directed to a gene which, when mutated, results in presence of many male flowers and absence of female flowers in watermelon. Plants comprising mutant alleles of this gene are useful as pollenizers in the production of triploid, seedless watermelon fruits.

Cancer immunology provides a desirable new approach for cancer treatment, but verifies that the potential neoantigens to be directed against targets are cost-effective and expensive. Analysis of MHC binding affinity, antigen processing, similarity to known antigens, predicted expression levels (as mRNA or proteins), self-similarity, and mutant allele frequency provides screening methods for identifying and prioritizing candidate neoantigens using sequencing data. The methods of the invention save time and money by identifying preferential candidate neoantigens for further experimental verification.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes (e.g, wherein each complex is of the exemplary formula shown below) comprising a phosphorodiamidate morpholino oligomer (e.g, useful for targeting DMD) covalently linked to an antibody (e.g., anti-TfR1 antibody). Also provided are uses of these formulations for treating a subject having a mutated DMD allele associated with Duchenne Muscular Dystrophy. (I)

The invention discloses a wild type gene amplification repression oligonucleotide sequence, a composition and application of the wild type gene amplification repression oligonucleotide sequence. The invention also discloses a competitive binding oligonucleotide sequence element which is competitively bound with a mutant allele site with the wild-type gene amplification repression oligonucleotide sequence, and when the competitive binding oligonucleotide sequence element is used together with the wild-type gene amplification repression oligonucleotide sequence disclosed by the invention, the mutant allele site is selectively bound with the mutant allele site. On the basis of the existing widely applied amplification blocker gene mutation detection method, the mutation enrichment efficiency can be greatly improved, the detection sensitivity of the amplification blocker gene mutation detection method is improved, and particularly, low-frequency and ultralow-frequency gene mutation can be stably and reliably detected in liquid biopsy commonly used in tumor precision medicine at present.

The present invention relates to a Lactuca sativa plant having delayed bolting and / or shade tolerance, wherein said plant comprises in its genome at least one copy of a mutant allele of the Phytochrome B (LsPhyB) gene. The present invention provides a seed from which the Lactuca sativa plant according to the present invention can be grown.

A forage sorghum plant or plant part comprising in its genome at least one mutant allele of a kafirin storage protein gene, which encodes a polypeptide comprising SEQ ID NO: 3. The mutant forage sorghum plant of the present disclosure has improved protein digestibility thus enhancing the quality of silage produced from the plant.