Abstract: The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.
Type:
Grant
Filed:
March 26, 2021
Date of Patent:
May 31, 2022
Assignee:
Beam Therapeutics Inc.
Inventors:
Ian Slaymaker, Nicole Gaudelli, Yi Yu, Bernd Zetsche, David A. Born, Seung-Joo Lee, Michael Packer
Abstract: Compositions for characterization of botulinum toxin (BoNT) are described that include a genetically modified cell that is transfected with an artificial construct comprising a nucleic acid sequence that encodes for a hybrid protein having (a) a reporter-containing portion chemically coupled to (b) a cleavage site and (c) a control fluorophore. The cleavage site interacts with a BoNT in a manner that cleaves the reporter-containing portion from remainder of the construct. The cleaved portion is destroyed or otherwise degraded by the local environment, and presence of BoNT is evidenced by reduction in signal from the reporter. The cleavage sequence is all or part of a SNARE protein, the cleavable reporter-containing portion is preferably Yellow Fluorescent Protein (YFP), Citrine, Venus, or a YPet protein and the control fluorophore is preferably CFP, mStrawberry, or a mCherry protein.
Abstract: The present invention relates to methods of providing a biomass residuum and compositions thereof. In particular examples, the biomass residuum includes one or more high value amino acids, even after removal of mixed alcohol components. In particular, the methods include implementing pre-treatment conditions and employing fermentation conditions including modified organisms.
Type:
Grant
Filed:
April 18, 2019
Date of Patent:
May 10, 2022
Assignee:
National Technology & Engineering Solutions of Sandia, LLC
Abstract: Compositions and methods are provided that reduce the time required for detection of botulinum neurotoxins in cell-based assays. In one aspect an isoquinolynyl compound can be used for this purpose. In such cell-based assays the cell can include an enzyme that facilitates degradation of the reporter significantly faster after the cleavage than before the cleavage, and presence of the Botulinum toxin correlates with reduction of the signal from a baseline signal. The cell can advantageously express both the construct that includes the reporter, and an enzyme that facilitates the degradation.
Abstract: The present disclosure relates to methods for increasing observed editing rates in the surviving bacteria cells. The compositions and methods presented herein in combination lead to a phenomenon of “edit or die.” Although less cells survive plating and editing, a large percentage of cells that do survive are multiple editors. In one experiment it was found that if a cell survives transformation, plating, and editing, 75% of the surviving cells are multiple editors; that is, 75% of the surviving cells were simultaneously edited with edits at two or more different locations within the bacterial genome.
Type:
Grant
Filed:
November 28, 2021
Date of Patent:
May 3, 2022
Assignee:
Inscripta, Inc.
Inventors:
Tian Tian, Eileen Spindler, Charles Johnson, Clint Davis
Abstract: The present invention provides engineered transglutamirase enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, methods of producing these enzymes, and methods of using the engineered transglutaminase enzymes.
Type:
Grant
Filed:
November 2, 2018
Date of Patent:
May 3, 2022
Assignee:
Codexis, Inc.
Inventors:
Jovana Nazor, Jie Yang, Goutami Banerjee, Xiyun Zhang, James Nicholas Riggins, Erika M. Milczek, Jeffrey C. Moore
Abstract: A method for recovering one or more water immiscible compounds comprising acidifying and disrupting the microbial biomass; heating the acidified, disrupted microbial biomass to form a heated, acidified disrupted microbial biomass; and contacting the heated, acidified, disrupted microbial biomass with a disulfonated surfactant in an amount sufficient to release at least 30% of the one or more water immiscible compounds from the microbial biomass.
Abstract: The present invention relates to methods of upgrading biomass to provide useful chemical intermediates, fuels, amino acids, nutrients, etc. In particular examples, the biomass is a by-product of ethanol production and is mainly used as high-protein feed. Described herein are methods for upgrading such biomass, such as by implementing pre-treatment conditions and by employing fermentation conditions including modified organisms.
Type:
Grant
Filed:
May 7, 2020
Date of Patent:
April 26, 2022
Assignee:
National Technology & Engineering Solutions of Sandia, LLC
Inventors:
Ryan Wesley Davis, Blake Simmons, Mary Bao Tran-Gyamfi, Benjamin Chiau-Pin Wu
Abstract: A new thermostable luciferase of the following mutant luciferase (a) or (b): (a) a mutant of a wild-type luciferase comprising the amino acid sequence of SEQ ID NO: 1, wherein phenylalanine at position 292 and/or phenylalanine at position 294 in the amino acid sequence of SEQ ID NO: 1 is substituted with another amino acid; or (b) a mutant of a luciferase having 93% or more homology with the amino acid sequence of SEQ ID NO: 1, wherein in the amino acid sequence of the mutant, the amino acid at a site corresponding to position 292 and/or position 294 in the amino acid sequence of SEQ ID NO: 1 is substituted with another amino acid.
Abstract: Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.
Type:
Grant
Filed:
December 17, 2021
Date of Patent:
April 19, 2022
Assignee:
Inscripta, Inc.
Inventors:
Andrew Garst, Ryan T. Gill, Tanya Elizabeth Warnecke Lipscomb
Abstract: An acid phosphatase mutant, and method for preparing nicotinamide riboside by same. The mutant is a protein of the following (a), (b) or (c): (a) a protein, having an amino acid sequence shown in SEQ ID NO: 3; (b) a protein, derived from (a), having catalytic activity higher than an acid phosphatase parent having an amino acid sequence shown in SEQ ID NO: 2, obtained by substituting, deleting or adding several amino acids in the amino acid sequence shown in SEQ ID NO: 3, using nicotinamide mononucleotide as a substrate; (c) a protein, having catalytic activity higher than the acid phosphatase shown in SEQ ID NO: 2, having 90% or more homology with the amino acid sequence of the protein defined by (a) or (b), and using nicotinamide mononucleotide as a substrate. It is used to prepare nicotinamide riboside and the conversion rate can be 99%.
Abstract: The present invention discloses A METHOD TO PRODUCE PROTEIN IN PENICILLIUM AMAGASAKIENSE'S SLEEPING SPORES BY TRANSFORMATION OF SSRNA. The method includes three steps of culture of Penicillium amagasakiense and collection of spores, pretreatment of Penicillium anagasakiense spores, and electroporation of Penicillium anagasakiense spores by using HDEN method. In the present invention, non-germinated spores are used as a starting material for introduction of exogenous molecules. The exogenous protein coding single stranded RNA is introduced into the resting spores of Penicillium amagasakiense by employing the HDEN electrotransformation technique to express protein. The method of this invention is simple and fast, the effect is excellent, and the transformation rate reaches more than 90%.
Abstract: Detergent compositions that include a lipase variant of a parent lipase which has lipase activity and includes one or more substitutions corresponding to G23S, D27N, A40, F51I,L, E56R, D57N, V60E,K, K98I, N101D, R118, G163S, T231R, N233R, Y220F, T244E, and P256T using SEQ ID NO: 2 for numbering. Water-soluble unit dose articles including water-soluble film and a detergent composition including lipase variants. Methods of cleaning and/or treatment of surfaces using such compositions.
Type:
Grant
Filed:
September 25, 2018
Date of Patent:
March 29, 2022
Assignee:
The Procter & Gamble Company
Inventors:
Steven George Patterson, Nazarmohammad Gulamhussain Momin, Miguel D. G. P. Toscano, Thomas A. Poulsen, Carsten H. Hansen, Lone Baunsgaard, Keith Gibson
Abstract: The activity of a number of therapeutic antibodies is mediated in part by antibody-dependent cell-mediated cytotoxicity (ADCC). An engineered effector cell line expressing the low affinity Fc receptor, Fc?R111a (CD16), that responds to ligation of the Fc moiety of antibody bound to the specific antigen expressed on target cells by activation of a NFAT responsive reporter gene is described. In this cell line the firefly luciferase (FL) reporter gene is regulated by a novel synthetic chimeric promoter containing binding sites for NF-AT, AP1, NFkB, and STAT5 that confers improved sensitivity, an improved dynamic range, an improved tolerance to human serum and a reduced incubation time, relative to engineered effector cell lines that express a NFAT regulated reporter-gene, when used in an ADCC assay together with engineered target cells.
Abstract: A method for preparing a hyper-cellulolytic catabolite derepressed mutants of ascomycetes fungus, especially variants of Penicillium funiculosum. Selection media used to isolate such variants include amorphous cellulose and a high concentration of glucose. Cellulase activities of mutant ID-10, in particular such as FPase and ?-glucosidase were 1.5 times higher than Penicillium funiculosum MRJ-16 (parent). Furthermore, fungal mutant morphology was changed and no pH adjustment was required throughout the enzyme production process.
Abstract: Provided is a method of producing ?-hydromuconic acid, the method including the step of culturing a microorganism belonging to the genus Serratia capable of producing ?-hydromuconic acid.
Abstract: The present invention relates to new plasma or new platelet-rich plasma preparations, new cell dissociation methods, new cell associations or compositions, a method of preparation thereof, a use thereof, devices for the preparation thereof and preparations containing such a platelet-rich plasma preparation and cell associations or compositions. Specifically, the invention provides plasma or platelet-rich plasma alone or in cell composition preparations for use in tissue regeneration and bone regeneration and pain reduction.
Abstract: The present disclosure relates to an adenylosuccinate synthetase variant, a microorganism containing the same, and a method for preparing purine nucleotides using the microorganism.
Type:
Grant
Filed:
August 23, 2018
Date of Patent:
February 1, 2022
Assignee:
CJ CHEILJEDANG CORPORATION
Inventors:
Min Ji Baek, Ji Hye Lee, So-jung Park, Jee Yeon Bae
Abstract: Disclosed herein are novel Pichia pastoris strains for expression of exogenous proteins with substantially homogeneous N-glycans. The strains are genetically engineered to include a mutant OCH1 allele which is transcribed into an mRNA coding for a mutant OCH1 gene product (i.e., ?-1,6-mannosyltransferase, or “OCH1 protein”). The mutant OCH1 protein contains a catalytic domain substantially identical to that of the wild type OCH1 protein, but lacks an N-terminal sequence necessary to target the OCH1 protein to the Golgi apparatus. The strains disclosed herein are robust, stable, and transformable, and the mutant OCH1 allele and the ability to produce substantially homogeneous N-glycans are maintained for generations after rounds of freezing and thawing and after subsequent transformations.