Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.
Abstract: Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.
Type:
Grant
Filed:
March 14, 2022
Date of Patent:
December 27, 2022
Assignees:
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, AGILENT TECHNOLOGIES, INC.
Inventors:
Matthew H. Porteus, Ayal Hendel, Joe Clark, Rasmus O. Bak, Daniel E. Ryan, Douglas J. Dellinger, Robert Kaiser, Joel Myerson
Abstract: The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.
Type:
Grant
Filed:
April 4, 2017
Date of Patent:
December 6, 2022
Assignee:
SNIPR TECHNOLOGIES LIMITED
Inventors:
Jasper Clube, Morten Sommer, Christian Grøndahl, Eric Van Der Helm, Ruben Vanquez-Uribe
Abstract: Nucleic acids encoding endogenous Gag peptides can be isolated from various organisms. Nucleic acids encoding various endogenous Gag polypeptides can be isolated from human DNA. The nucleic acids can be used to express endogenous Gag polypeptides that can be assembled into capsids. Endogenous Gag polypeptides and capsids can be used package cargo and/or deliver it to cells, for example, to package and/or deliver a nucleic acid molecule for use in gene editing, such as a component involved in a CRISPR-Cas system.
Type:
Grant
Filed:
July 21, 2021
Date of Patent:
November 22, 2022
Assignee:
VNV NEWCO INC.
Inventors:
Colin Malone, Ian Peikon, Zachary Gilbert, Andrey Pisarev, Adam Fraites, Jessica Crisp
Abstract: Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.
Type:
Grant
Filed:
December 18, 2020
Date of Patent:
November 8, 2022
Assignee:
Amicus Therapeutics, Inc.
Inventors:
Hung Do, Steven Tuske, Russell Gotschall, Ce Feng Liu
Abstract: The present invention provides a therapy for treating loss of GABA-mediated pre-synaptic inhibition after spinal injury. The therapeutic regimen includes spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) and VGAT (vesicular GABA transporter) to modulate chronic spasticity in patients after spinal traumatic or ischemic injury.
Type:
Grant
Filed:
March 27, 2017
Date of Patent:
October 18, 2022
Assignee:
The Regents of the University of California
Abstract: This invention pertains to modified compositions for use in CRISPR systems, and their methods of use. In particular, length-modified and chemically-modified forms of crRNA and tracrRNA are described for use as a reconstituted guide RNA for interaction with Cas9 of CRISPR systems. The resultant length-modified and chemically-modified forms of crRNA and tracrRNA are economical to produce and can be tailored to have unique properties relevant to their biochemical and biological activity in the context of the CRISPR Cas9 endonuclease system.
Type:
Grant
Filed:
October 21, 2016
Date of Patent:
October 4, 2022
Assignee:
INTEGRATED DNA TECHNOLOGIES, INC.
Inventors:
Michael Allen Collingwood, Ashley Mae Jacobi, Garrett Richard Rettig, Mollie Sue Schubert, Mark Aaron Behlke
Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), RNA control devices, and destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) or other transgenes in eukaryotic cells. Multicistronic vectors are also disclosed for use in engineering host eukaryotic cells with the CARs and transgenes under the control of the control devices. These control devices can be used to optimize expression of CARs in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered after stimulation of the CAR on the eukaryotic cell.
Abstract: The present invention is directed to methods and compositions for targeted gene silencing that provide the ability to not only repress expression but to modulate the repression of expression of one or more target genes. In one aspect, a recombinant nucleic acid molecule is provided comprising a nucleotide sequence encoding a subset of CRISPR-cas polypeptides, or functional fragments thereof, from a type-I CRISPR-cas system. In some aspects, a recombinant nucleic acid of the invention comprises a nucleotide sequence encoding three or more Type I Cascade polypeptides having substantial identity to a type I Cascade polypeptide.
Abstract: The invention described herein provides compositions and reagents for assembling a tripartite complex at a specific location of a target DNA. The invention also provides methods for using the complex to, for example, label a specific genomic locus, to regulate the expression of a target gene, or to create a gene regulatory network.
Type:
Grant
Filed:
September 13, 2017
Date of Patent:
September 6, 2022
Assignee:
The Jackson Laboratory
Inventors:
Haoyi Wang, Albert Cheng, Nathaniel Jillette
Abstract: The present disclosure provides viral microparticles comprising genetically-engineered baculoviruses (at least partially) embedded in a polymeric matrix for the local delivery of therapeutic nucleic acid molecules to the cells of a vertebrate individual (optionally in combination with a medical implant such as vascular stent platform). The viral microparticles are especially useful for promoting the healing of a wound as well as the repair of a blood vessel and prevent pathological scarring. Also provided herein are processes for making the viral microparticles, pharmaceutical compositions comprising viral microparticles as well as supports comprising the viral microparticles for the locating the viral microparticles in a wound or in the vicinity of a wound.
Abstract: Disclosed herein are polynucleotides having a plurality of thymine nucleotides and an endonuclease recognition site inserted therein, methods of engineering the polynucleotides having a plurality of thymine nucleotides and an endonuclease recognition site inserted therein, and methods of enhancing transcription, translation, and increasing stability of a polynucleotide.
Type:
Grant
Filed:
April 11, 2018
Date of Patent:
August 2, 2022
Assignee:
SEATTLE CHILDREN'S HOSPITAL
Inventors:
Andrew M. Scharenberg, Kyle Jacoby, Alexandra E. Grier
Abstract: The invention is directed to methods for determining antigen-specific T cells generally and to T cell receptors which bind an epitope of the Wilms' tumor antigen-1 (WT1) protein specifically. The disclosure also provides polynucleotides encoding the TCRs, engineered cells exogenously expressing the TCRs, and methods of making and using the TCRs and/or cells expressing the TCRs.
Type:
Grant
Filed:
June 13, 2018
Date of Patent:
July 19, 2022
Assignee:
Adaptive Biotechnologies Corporation
Inventors:
Marcos E. Milla, Mark Klinger, Peter J. R. Ebert, Timothy Lee Hayes, Edward J. Osborne, Joyce K. Hu
Abstract: Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in insect cells. In some embodiments, methods and compositions include the use of modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles.
Type:
Grant
Filed:
April 16, 2017
Date of Patent:
July 12, 2022
Assignee:
University of Florida Research Foundation, Incorporated
Abstract: The present invention relates to modified adeno-associated virus (AAV) vectors for use in transducing a cell in the central nervous system (CNS) of a subject, and for use in the prevention or treatment of a CNS disease. In particular, the modified AAV vectors according to the present invention comprise at least one surface-bound saccharide, and are to be administered directly to the CNS but not intracerebroventricularly.
Abstract: The present disclosure provides an automated method of producing genetically modified immune cells, including chimeric antigen receptor T (CAR T) cells, utilizing a fully-enclosed cell engineering system.
Inventors:
Yaling Shi, Erika McAfee, Samatha Bandapalle, Ann Siehoff, Timo Gleissner, Joseph O'Connor, Eytan Abraham, Kelly Purpura, Nuala Trainor, Timothy Smith
Abstract: Compositions and methods are provided for rapid characterization of Cas endonuclease systems and the elements comprising such systems, including, but not limiting to, rapid characterization of PAM sequences, guide RNA elements and Cas endonucleases. Type II Cas9 endonuclease systems originating from Brevibacillus laterosporus, Lactobacillus reuteri Mlc3, Lactobacillus rossiae DSM 15814, Pediococcus pentosaceus SL4, Lactobacillus nodensis JCM 14932, Sulfurospirillum sp. SCADC, Bifidobacterium thermophilum DSM 20210, Loktanella vestfoldensis, Sphingomonas sanxanigenens NX02, Epilithonimonas tenax DSM 16811, Sporocytophaga myxococcoides are described herein. The present disclosure also describes methods for genome modification of a target sequence in the genome of a cell, for gene editing, and for inserting a polynucleotide of interest into the genome of a cell.
Type:
Grant
Filed:
May 12, 2016
Date of Patent:
June 28, 2022
Inventors:
Andrew Mark Cigan, Giedrius Gasiunas, Tautvydas Karvelis, Virginijus Siksnys, Joshua K Young
Abstract: Described herein are recombinant AAV vectors comprising a polynucleotide sequence comprising ?-sarcoglycan and methods of using the recombinant vectors to reduce or prevent fibrosis in a mammalian subject suffering from a muscular dystrophy. Also described herein are combination therapies comprising administering AAV vector(s) expressing ?-sarcoglycan and miR-29c to a mammalian subject suffering from a muscular dystrophy.
Type:
Grant
Filed:
April 14, 2017
Date of Patent:
June 14, 2022
Assignee:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Abstract: An Aureobasidium pullulans recombinant strain with high-yield heavy oil and a construction method and application thereof are provided. The Aureobasidium pullulans recombinant strain is obtained by knocking out a pullulan synthetase PUL gene while overexpressing an ACL gene. The obtained Aureobasidium pullulans recombinant strain can significantly increase the yield of heavy oil. After 7-day fermentation with xylose as carbon source, the yield of the heavy oil of the recombinant strain reaches 19.4372 g/L, while the yield of the heavy oil of the original strain is 10.0325 g/L, i.e. the recombinant strain improves the yield by 93.74% compared with the original strain.
Type:
Grant
Filed:
October 15, 2020
Date of Patent:
June 7, 2022
Assignee:
Tianjin University of Science and Technology