Abstract: The invention provides particle compositions having applications in nucleic acid analysis. Nucleic acid polymer particles of the invention allow polynucleotides to be attached throughout their volumes for higher loading capacities than those achievable solely with surface attachment. In one aspect, nucleic acid polymer particles of the invention comprise polyacrylamide particles with uniform size distributions having low coefficients of variations, which result in reduced particle-to-particle variation in analytical assays. Such particle compositions are used in various amplification reactions to make amplicon libraries from nucleic acid fragment libraries.
Type:
Application
Filed:
September 4, 2018
Publication date:
March 7, 2019
Inventors:
Wolfgang HINZ, John LEAMON, David LIGHT, Jonathan M. ROTHBERG
Abstract: The present invention relates to compositions and methods for identifying, assessing, preventing, and treating cancer and modulating immune responses using SLNCR isoforms.
Abstract: The present invention provides lipid-based formulations for delivering, e.g., introducing, nucleic acid-lipid particles comprising an interference RNA molecule to a cell, and assays for optimizing the delivery efficiency of such lipid-based formulations.
Type:
Application
Filed:
March 26, 2018
Publication date:
March 7, 2019
Inventors:
Ian MacLachlan, Lorne R. Palmer, James Heyes
Abstract: The application relates to methods of treatment and treatment regimens for Alpha-1 Antitrypsin deficiency (AATD) and the conditions, manifestations, and diseases caused by AATD, by the administration of one or more expression-inhibiting oligomeric compounds having a nucleobase sequence complementary to a coding sequence in the Alpha-1 Antitrypsin (A1AT or AAT) gene that inhibits the expression of the AAT gene, in combination with one or more autophagy enhancing agents that enhance and/or induce the endogenous autophagy mechanism to facilitate and encourage clearance of polymerized mutant AAT protein accumulated in the endoplasmic reticulum of hepatocytes.
Type:
Application
Filed:
August 9, 2018
Publication date:
March 7, 2019
Inventors:
Christine I. Wooddell, Ryan M. Peterson, Peter B. Leone
Abstract: The present disclosure provides filler or stuffer sequences, compositions thereof including expression cassettes and vectors, such as viral (e.g., AAV) vectors and methods of delivering a therapeutic agent to a mammal and/or treating a disease.
Type:
Application
Filed:
March 17, 2017
Publication date:
March 7, 2019
Applicant:
The Children's Hospital of Philadelphia
Inventors:
Beverly L. DAVIDSON, Alejandro Mas MONTEYS, Megan S. KEISER
Abstract: The invention provides pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 17 nucleobases which are complementary to human microRNAs. The short oligonucleotides are particularly effective at alleviating miRNA repression in vivo. It is found that the incorporation of high affinity nucleotide analogues into the oligonucleotides results in highly effective anti-microRNA molecules which appear to function via the formation of almost irreversible duplexes with the miRNA target, rather than RNA cleavage based mechanisms, such as mechanisms associated with RNaseH or RISC.
Type:
Application
Filed:
September 10, 2018
Publication date:
March 7, 2019
Inventors:
Joacim Elmen, Phil Kearney, Sakari Kauppinen
Abstract: A composition for treating a lysogenic virus, including a vector encoding isolated nucleic acid encoding two or more gene editors chosen from gene editors that target viral DNA, gene editors that target viral RNA, and combinations thereof. A composition for treating a lytic virus, including a vector encoding isolated nucleic acid encoding at least one gene editor that targets viral DNA and a viral RNA targeting composition. A composition for treating both lysogenic and lytic viruses, including a vector encoding isolated nucleic acid encoding two or more gene editors that target viral RNA. A composition for treating lytic viruses. A method of increasing specificity of gene editors in treating an individual for a virus. Methods of treating a lysogenic virus or a lytic virus, by administering the above compositions to an individual having a virus and inactivating the virus.
Abstract: The present invention provides methods of treatment using inhibitors of DEK protein and DEK activity. Such methods include, but are not limited to, methods of preventing, treating, and/or ameliorating inflammatory diseases, infections, autoimmune diseases, malignant diseases, and other diseases or conditions in which DEK has been implicated. Such inhibitors of DEK protein include, but are not limited to, pharmaceutical compositions including single stranded DNA or RNA aptamers capable of binding to DEK. In some embodiments, such aptamers are useful for diagnosing DEK related diseases or conditions. Related kits and compositions are further provided.
Type:
Application
Filed:
November 15, 2018
Publication date:
March 7, 2019
Inventors:
David Markovitz, Nirit Mor-Vaknin, Maureen Legendre, David Engelke, Kristine Benford, Dave Pai
Abstract: RNA interference is provided for inhibition of HIF1A mRNA expression for treating patients with ocular angiogenesis, particularly for treating retinal edema, diabetic retinopathy, sequela associated with retinal ischemia, posterior segment neovascularization (PSNV), and neovascular glaucoma, and for treating patients at risk of developing such conditions.
Abstract: Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.
Type:
Application
Filed:
August 7, 2018
Publication date:
March 7, 2019
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Susan M. FREIER, Rosanne M. Crooke, Mark J. Graham, Kristina M. Lemonidis, Diane Tribble, Sanjay Bhanot, Andrew T. Watt
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of DYRKIB in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease or disorder in an individual in need.
Type:
Application
Filed:
March 16, 2017
Publication date:
March 7, 2019
Applicant:
Ionis Pharmaceuticals, Inc.
Inventors:
Brett P. Monia, Shuling Guo, Susan F. Murray
Abstract: Panels, compositions, and methods for treating cancer in a subject in need thereof are disclosed involving one or more genes the suppression of which renders the cancer chemosensitive and/or radiosensitive.
Type:
Application
Filed:
November 2, 2018
Publication date:
March 7, 2019
Inventors:
Nikolai Khodarev, Ravi Sood, Bernard Roizman, Ralph Weichselbaum
Abstract: The present invention relates to a novel method, expression vectors, and host cells for producing nicotinic acid riboside by regulating the pathways that lead to the production of nicotinic acid riboside.
Abstract: Disclosed are methods of gene delivery using capsid-modified recombinant adeno-associated viral (rAAV) particles. Exemplary methods are provided employing rAAV particles that have altered affinity for heparin or heparin sulfate. Also provided by the disclosure are methods employing the rAAV vector-based compositions, virus particles, host cells, and pharmaceutical formulations in the expression of selected therapeutic genes, proteins, polypeptides, peptides, antisense oligonucleotides, and/or ribozymes in selected mammals, including organs, tissues, and human host cells.
Type:
Application
Filed:
February 24, 2017
Publication date:
March 7, 2019
Applicant:
University of Florida Research Foundation, Incorporated
Inventors:
Nicholas Muzyczka, Kenneth H. Warrington, Marina Gorbatyuk, Oleg Gorbatyuk
Abstract: The present invention relates to stabilization of RNA, in particular mRNA, and an increase in mRNA translation. The present invention particularly relates to a modification of RNA, in particular in vitro-transcribed RNA, resulting in increased transcript stability and/or translation efficiency. According to the invention, it was demonstrated that certain sequences in the 3?-untranslated region (UTR) of an RNA molecule improve stability and translation efficiency.
Type:
Application
Filed:
October 5, 2016
Publication date:
March 7, 2019
Inventors:
Alexandra Orlandini Von Niessen, Stephanie Fesser, Britta Vallazza, Tim Beissert, Andreas Kuhn, Ugur Sahin, Marco Alexander Poleganov
Abstract: The disclosure provides nucleic acid molecules, including cDNA, comprising an alteration that encodes variant human Solute Carrier Family 14 Member 1 (SLC14A1) proteins that associate with protection against coronary artery disease (CAD). The disclosure also provides methods for classifying subjects at risk of developing a coagulation condition, based on the identification of such alterations.
Abstract: The present invention provides information on a mutant xylose isomerase gene and a mutant protein with which it is possible to impart high xylose metabolic capacity to budding yeast. Also provided is a yeast strain having the mutant xylose isomerase gene. Additionally provided is an efficient method for producing a useful substance using the yeast strain. The present invention provides mutant Clostridium-phytofermentans-derived xylose isomerase (CpXI) having high xylose metabolic activity, the CpXI comprising an amino acid sequence corresponding to an amino acid sequence in which the number 63 threonine of SEQ ID NO: 11 of CpXI is substituted by isoleucine, lysine, glycine, or histidine and/or the number 162 valine is substituted by alanine.
Type:
Application
Filed:
March 24, 2017
Publication date:
March 7, 2019
Applicant:
National Institute of Advanced Industrial Science and Technology
Abstract: Mutation of the rice ortholog of the Arabidopsis MTF1 gene results in increased rice transformation. CRISPR was used to generate several different mutations in the rice MTF1 gene. Agrobacterium-mediated transformation of these homozygous mutants indicated 5- to 10-fold increased transient and stable transformation, using GUS and luciferase assays.
Abstract: This disclosure relates to the field of secondary metabolite production in plants. More specifically, the disclosure relates to chimeric genes and their use in the regulation of biosynthesis and/or production of secondary metabolites in plants and plant-derived cell cultures.
Abstract: The present invention discloses mutations in the genes encoding starch synthases and also in starch branching enzymes associated with enhanced dietary fibre and resistant starch levels in the endosperm of a suitable variety of rice. The dietary fiber and resistant starch are enhanced to an extent to significantly reduce the hydrolysis index values of the rice grains to 35%-40%. These rice varieties are in great demand for diabetic population and provide a number of other health benefits such as reduced body weight gain, cardiac health and colon health. As this strategy does not involve the use of genetic manipulation technologies, it can be directly employed in the rice breeding programmers without any restrictions.
Abstract: Compositions and methods for modifying genomic DNA sequences are provided. The methods produce double-stranded breaks (DSBs) at pre-determined target sites in a genomic DNA sequence, resulting in mutation, insertion, and/or deletion of DNA sequences at the target site(s) in a genome. Compositions comprise DNA constructs comprising nucleotide sequences that encode a Cpf1 or Csm1 protein operably linked to a promoter that is operable in the cells of interest. The DNA constructs can be used to direct the modification of genomic DNA at pre-determined genomic loci. Methods to use these DNA constructs to modify genomic DNA sequences are described herein. Additionally, compositions and methods for modulating the expression of genes are provided.
Abstract: The disclosure provides DNA compositions that relate to transgenic insect resistant maize plants. Also provided are assays for detecting the presence of the maize DP-033121-3 event based on the DNA sequence of the recombinant construct inserted into the maize genome and the DNA sequences flanking the insertion site. Kits and conditions useful in conducting the assays are provided.
Type:
Application
Filed:
September 12, 2018
Publication date:
March 7, 2019
Applicants:
E. I. DU PONT DE NEMOURS AND COMPANY, PIONEER HI-BRED INTERNATIONAL, INC.
Inventors:
MARY BEATTY, KENT BRINK, VIRGINIA CRANE, SCOTT DIEHN, ALBERT L. LU, GREGORY J. YOUNG
Abstract: Methods and compositions are provided which employ a silencing element that, when ingested by a pest, such as a Pentatomidae plant pest, decrease the expression of a target sequence in the pest. The present invention provides various target polynucleotides set forth in any one of SEQ ID NOS: 6-12, 18-40 or active variants and fragments thereof, wherein a decrease in expression of one or more the sequences in the target pest controls the pest (i.e., has insecticidal activity). Plants, plant part, bacteria and other host cells comprising the silencing elements or an active variant or fragment thereof of the invention are also provided.
Type:
Application
Filed:
November 16, 2018
Publication date:
March 7, 2019
Applicant:
E. I. DU PONT DE NEMOURS AND COMPANY
Inventors:
Brian McGonigle, James Kevin Presnail, Navdeep Mutti
Abstract: The invention provides expression vectors and host cells for high-level expression of recombinant proteins. The expression vectors comprise Chinese hamster ovary elongation factor 1-? (CHEF1) transcriptional regulatory DNA elements and a cytomegalovirus (CMV) promoter and/or a human adenovirus tripartite leader (AdTPL) sequence. The invention achieves increased protein expression and better productivity of host cells compared to previously described expression systems.
Abstract: The present invention relates to nucleic acid molecules which are capable of promoting transcription of operably-linked heterologous polynucleotides in mammalian ceils. The invention also relates to expression vectors and host ceils which comprise the nucleic acid molecules of the invention. Such expression vectors may be used to produce recombinant proteins, e.g. antibodies and lentiviral polypeptides.
Type:
Application
Filed:
February 28, 2017
Publication date:
March 7, 2019
Applicant:
OXFORD GENETICS LIMITED
Inventors:
Ryan CAWOOD, Richard PARKER-MANUEL, Weiheng SU
Abstract: Some embodiments of the methods and compositions provided herein relate to the preparation surfactant protein-D (SP-D). Some embodiments include the expression of human SP-D in certain cell lines, and the purification of human SP-D from such cell lines. Some embodiments include the preparation of certain oligomeric forms of human SP-D.
Type:
Application
Filed:
September 4, 2018
Publication date:
March 7, 2019
Inventors:
Jan Susan Rosenbaum, Frederick Gyapon Quast, Matthias Kaup, Lars Stöckl
Abstract: Some embodiments of the methods and compositions provided herein relate to the preparation surfactant protein-D (SP-D). Some embodiments include the expression of human SP-D in certain cell lines, and the purification of human SP-D from such cell lines. Some embodiments include the preparation of certain oligomeric forms of human SP-D.
Type:
Application
Filed:
September 4, 2018
Publication date:
March 7, 2019
Inventors:
Jan Susan Rosenbaum, Frederick Gyapon Quast, Matthias Kaup, Lars Stöckl
Abstract: An intracellular delivery system and method are provided. The intracellular delivery system comprises a laser-activated surface and cells positioned at a distance from the laser-activated surface. A laser provided a laser pulse that is used to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells. The method of intracellular delivery comprises positioning a laser-activated surface at a distance from cells and applying a laser pulse from the laser to the surface to porate membranes of the cells to deliver or extract cargo from the cells into a liquid surrounding the cells.
Abstract: The present disclosure relates to using a source of one or more monosaccharides derived from a pulp or paper mill waste by-product for propagating microorganisms (e.g., yeast or bacteria). If desired, after propagation, the microorganisms can then be used to ferment one or more monosaccharides derived from a pulp or paper mill waste by-product into one or more biochemicals. Optionally, a stillage composition can be included in propagation medium to facilitate propagation and/or a stillage composition can be used to facilitate enzymatic hydrolysis of oligosaccharides and/or polysaccharides in a pulp or paper mill waste by-product to form monosaccharides.
Type:
Application
Filed:
September 5, 2018
Publication date:
March 7, 2019
Inventors:
Cory J. Sarks, Alex C. Johnson, Malgorzata M. Slupska, Zachary J. Karl, Melanie A. Eichmann
Abstract: A method of producing lipids, containing the steps of: culturing a transformant wherein the expressions of a gene encoding any one of the following proteins (A) to (F) and a gene encoding an acyl-ACP thioesterase are enhanced, and producing fatty acids or lipids containing these fatty acids as components: (A) a protein consisting of the amino acid sequence set forth in SEQ ID NO: 2; (B) a protein consisting of an amino acid sequence having 89% or more identity with the amino acid sequence of the protein (A), and having acyl-CoA synthetase activity; (C) a protein consisting of the amino acid sequence set forth in SEQ ID NO: 4; (D) a protein consisting of an amino acid sequence having 49% or more identity with the amino acid sequence of the protein (C), and having acyl-CoA synthetase activity; (E) a protein consisting of the amino acid sequence set forth in SEQ ID NO: 6; and (F) a protein consisting of an amino acid sequence having 85% or more identity with the amino acid sequence of the protein (E), a
Abstract: A recombinant strain of F. diplosiphon was made by transforming wild type F. diplosiphon with a pGEM-7Zf (+) plasmid containing sterol desaturase gene (SD) via electroporation. The recombinant strain was designated B481-SD and overexpressed the sterol desaturase gene to result in enhanced lipid production. Selection made on NaCl enabled growth of the transformant to thrive up to 50 g L?1 NaCl. This strain was designated B481-SDH.
Abstract: Using as a carbon source a long chain fatty acid which has not necessarily been efficaciously used in industry, culture of a microorganism and production of a substance by the microorganism are industrially efficiently carried out. A microorganism is cultured in the presence of a carbon source including anyone of the following compositions: (1) a fatty acid composition containing at least two fatty acids selected from the group consisting of lauric acid, myristic acid, palmitic acid and oleic acid; and (2) a mixed composition containing at least one fatty acid selected from the group consisting of lauric acid, myristic acid, palmitic acid and oleic acid, and a fat and oil, and having a content of the fatty acid of not less than 10% by weight.
Abstract: Aspects of the invention include host cells that are engineered to produce benzylisoquinoline alkaloids (BIAs). The host cells include heterologous coding sequences for a variety of enzymes involved in synthetic pathways from starting compounds to BIAs of the host cell. Also provided are methods of producing the BIAs of interest by culturing the host cells under culture conditions that promote expression of enzymes encoded by the heterologous coding sequences of the host cells. Aspects of the invention further include compositions, e.g., host cells, starting compounds and kits, etc., that find use in methods of the invention.
Type:
Application
Filed:
November 14, 2018
Publication date:
March 7, 2019
Inventors:
Christina D. Smolke, Catherine Thodey, Isis Trenchard, Stephanie Galanie
Abstract: The present disclosure relates to polypeptides having transaminase activity, polynucleotides encoding the polypeptides, and methods of using the polypeptides.
Type:
Application
Filed:
November 19, 2018
Publication date:
March 7, 2019
Inventors:
Christopher K. Savile, Emily Mundorff, Jeffrey C. Moore, Paul N. Devine, Jacob M. Janey
Abstract: A composition includes a sugar source and inositol. The sugar source is one more sugars select from the group consisting of glucose, sucrose, sucrolose, tagatose, galactose, high fructose corn syrup, fructose, isoglucose, and rhamnose. The composition of sugar and inositol has an unique properties that prevents or limits the signaling of TNF-? and associated pro-inflammatory cytokines when metabolized by an individual consuming the composition. Accordingly, the composition can be advantageously used to control blood glucose levels, treat diabetes and related conditions as well as treat diseases based on an inflammatory response.
Abstract: Methods for in vitro transcription and translation from an RCA product are provided. The methods comprise providing a double-stranded RCA product, wherein the double-stranded RCA product consists essentially of tandem repeats of a minimalistic expression sequence. The methods further comprise expressing a protein from the double-stranded RCA product in a cell-free expression system.
Type:
Application
Filed:
July 20, 2018
Publication date:
March 7, 2019
Inventors:
John Richard Nelson, Robert Scott Duthie, Erik Leeming Kvam, Wei Gao
Abstract: Provided herein include methods of making mogroside compounds, e.g., Compound 1, compositions (for example host cells) for making the mogroside compounds, and the mogroside compounds made by the methods disclosed herein, and compositions (for example, cell lysates) and recombinant cells comprising the mogroside compounds (e.g., Compound 1). Also provided herein are novel cucurbitadienol synthases and the use thereof.
Type:
Application
Filed:
May 2, 2018
Publication date:
March 7, 2019
Inventors:
Andrew P. Patron, Chris Edano Noriega, Rama R. Manam, Justin Colquitt, Nathan Faber, Helge Zieler, Justin Stege
Abstract: A method for increasing production of a polypeptide in a bacterial cell in culture is provided. The method can comprise contacting a bacterial cell in a culture medium with an amount of an albumin polypeptide sufficient to induce an increase in accumulation of the polypeptide in the bacterial cell and/or an increase in secretion of the polypeptide from the bacterial cell into the culture medium relative to a bacterial cell grown in a culture medium in the absence of the albumin polypeptide. The bacterial cell can be a Bordetella species cell, optionally wherein the Bordetella species cell is a Bordetella pertussis cell, a Bordetella bronchiseptica cell or a Bordetella parapertussis cell. Kits, vaccine production methods, screening methods and therapeutic methods are also disclosed.
Type:
Application
Filed:
April 4, 2017
Publication date:
March 7, 2019
Inventors:
Erik L. Hewlett, Mary C. Gray, Laura A. Gonyar
Abstract: The invention features methods panels, cartridges, and systems for detecting pathogens and for diagnosing and treating diseases, including bacteremia and sepsis.
Type:
Application
Filed:
January 20, 2017
Publication date:
March 7, 2019
Inventors:
Ulrich Hans THOMANN, Lori Anne NEELY, Heidi Susanne GIESE, Jessica Ann TOWNSEND, Rahul Krishan DHANDA, Thomas Jay LOWERY, Jr., Urvi VED, Brendan MANNING, Nu Ai PHUNG, Joanne Lawton GARVER, Benjamin B. STONE
Abstract: A collection broth used for recovering microorganisms on a surface is provided. The collection broth includes a buffering system and a neutralization system. All components of the collection broth are both food-grade and hypoallergenic.
Abstract: A method of preparing a sample for cytometry detection of viable biological contaminants includes obtaining a non-aqueous sample, obtaining a suitable solvent, and filtering the suitable solvent creating a filtered solvent. The non-aqueous sample is combined with the filtered solvent creating a mixture for cytometry testing.
Abstract: This invention provides methods for treating diseases associated with elevated p38 mitogen-activated protein kinase activity. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.
Type:
Application
Filed:
March 26, 2018
Publication date:
March 7, 2019
Applicant:
The Tructees Of The University Of Pennsylvania
Abstract: The present disclosure provides methods and systems for amplifying and analyzing nucleic acid samples. The present disclosure provides methods for preparing cDNA and/or DNA molecules and cDNA and/or DNA libraries using modified reverse transcriptases.
Abstract: Lyophilized biological reagents, such as enzymes (e.g., PCR reagents) and antibodies, are provided that include a wax component. Thus, in some aspects, a method is provided for storing a biological reagent comprising formulating the reagent into a lyophilized composition including a wax component. Methods for using such lyophilized reagents are likewise provided.
Abstract: A method for real-time quantitative detection of single-type, target nucleic acid sequences amplified using a PCR in a microwell, comprising introducing in the microwell a sample comprising target nucleic acid sequences, magnetic primers, and labelling probes; performing an amplification cycle to form labelled amplicons; attracting the magnetic primers to a surface through a magnetic field to form a layer including labelled amplification products and free magnetic primers; and detecting the labelled amplification products in the layer with a surface-specific reading method.
Type:
Application
Filed:
November 5, 2018
Publication date:
March 7, 2019
Inventors:
Lucio Renna, Clelia Carmen Galati, Natalia Maria Rita Spinella
Abstract: Provided herein are aptamers, aptamer probes and biosensor systems that detect C. difficile glutamate dehydrogenase (GDH). Also provided are methods of detecting C. difficile GDH using the aptamers, probes and biosensors and methods of determining whether a subject has a C. difficile infection.
Abstract: The invention provides methods for binding to and protecting target nucleic acid directly from plasma without the need for certain complex sample preparation steps, using catalytically active Cas endonuclease. The catalytically active Cas endonucleases, along with their sequence-specific guide RNAs, may be introduced directly into the plasma sample, where the catalytically active Cas endonucleases bind to ends of a target nucleic acid. The target nucleic acid is thus isolated or enriched in a sequence-specific manner. The target nucleic acid may then be subject to any suitable detection or analysis assay, such as amplification or sequencing. The bound catalytically active Cas proteins prevent exonuclease from digesting the target nucleic acid in a plasma sample leaving only the target nucleic acid substantially present in the enriched sample.