Abstract: This disclosure provides methods of downregulating or eliminating gene expression of one or more Dynamic Influencer of Gene expression (DIG) and/or one or more DIG-like (DIL) sequences in plants and plant cells, as well as constructs and compositions useful in such methods. Such recombinant plants can have decreased abscisic acid (ABA) sensitivity, decreased salt sensitivity, or both.
Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.
Type:
Grant
Filed:
November 22, 2016
Date of Patent:
February 9, 2021
Assignee:
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
Ronald M. Evans, Eiji Yoshihara, Michael R. Downes, Ruth T. Yu, Annette R. Atkins
Abstract: The present disclosure provides FGF1 mutant proteins, which selectively bind to/activate FGFR1b. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed FGF1 mutants to reduce blood glucose in a mammal and treat a metabolic disorder are provided.
Type:
Application
Filed:
July 15, 2020
Publication date:
February 4, 2021
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Sihao Liu, Ruth T. Yu
Abstract: Provided herein are compounds and compositions useful in increasing PPAR? activity. The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
Type:
Grant
Filed:
November 13, 2019
Date of Patent:
February 2, 2021
Assignees:
Mitobridge, Inc., The Salk Institute for Biological Studies
Inventors:
Michael Downes, Ronald M. Evans, Arthur Kluge, Bharat Lagu, Masanori Miura, Sunil Kumar Panigrahi, Michael Patane, Susanta Samajdar, Ramesh Senaiar, Taisuke Takahashi
Abstract: Tumor-selective recombinant adenoviruses that possess deletions or modifications in the E3 region are described. Recombinant adenoviruses that express adenovirus death protein (ADP) but have a deletion of at least three of the remaining six E3 genes exhibit enhanced virus replication. The recombinant adenoviruses further include additional modifications to allow selective replication in tumor cells and to detarget viruses from the liver. Use of the recombinant adenoviruses for cancer treatment is described.
Type:
Application
Filed:
October 9, 2020
Publication date:
January 28, 2021
Applicant:
Salk Institute for Biological Studies
Inventors:
Clodagh O'Shea, Michael Lyman, William Partlo, Shigeki Miyake-Stoner
Abstract: Methods, devices, and systems are disclosed for producing cognitive and/or sensory profiles. In one aspect, a method to provide a cognitive or sensory assessment of a subject includes selecting a profile category from among a cognitive performance profile, a sensory performance profile, and a cognitive and sensory performance profile, presenting a sequence of stimuli to a subject, the sequence of stimuli based on the selected profile category, acquiring physiological signals of the subject before, during, and after the presenting the sequence of stimuli to produce physiological data, and processing the physiological data to generate an information set including one or more quantitative values associated with the selected profile category.
Type:
Grant
Filed:
January 24, 2018
Date of Patent:
January 12, 2021
Assignees:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
Todd Prentice Coleman, Rui Ma, Sanggyun Kim, Cheolsoo Park, Ricardo Gil Da Costa, Raynard Fung, Diego Mesa
Abstract: Provided herein is the use of compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), alone or in combination with other therapeutic agents, in the treatment of human immunodeficiency virus (HIV).
Type:
Grant
Filed:
May 24, 2019
Date of Patent:
December 15, 2020
Assignees:
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE, SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
Lars Pache, Sumit K. Chanda, Mitchell Dennis Vamos, Nicholas David Peter Cosford, Peter Teriete, John Marlett, Arturo Diaz, John A. T. Young
Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.
Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.
Abstract: Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.
Abstract: Provided herein are, inter alia, are media compositions useful for culturing neural cells. In particular, the compositions provided herein mimic important physiological conditions in the living brain and sustain neural activity. The media compositions provided herein improve the efficiency of human neuron maturation and promote synaptic function in long-term in vitro cultures.
Abstract: Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.
Type:
Grant
Filed:
September 10, 2019
Date of Patent:
October 27, 2020
Assignees:
Salk Institute for Biological Studies, The University of Sydney
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Sungsoon Fang, Jae Myoung Suh, Thomas J. Baiga, Ruth T. Yu, John F. W. Keana, Christopher Liddle
Abstract: The invention provides compositions featuring TRP-4 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRP-4 polypeptide in neurons and other cell types using ultrasound.
Abstract: Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.
Type:
Application
Filed:
June 30, 2020
Publication date:
October 15, 2020
Applicant:
Salk Institute for Biological Studies
Inventors:
Clodagh O'Shea, William Partlo, Colin Powers
Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.
Abstract: Disclosed are probes that are expressed in a cell to label an intracellular target (such as protein or DNA) for both light and electron microscopy. The probes comprise a targeting domain that specifically binds to the intracellular target, a detection tag that can be used to detect the intracellular location of the probe using light microscopy, and a ferritin nanoparticle ferritin nanoparticle with ferroxidase activity and that stores ferric oxide. Also disclosed are nucleic acids encoding the fusion proteins and methods of their use.
Abstract: In certain aspects, the invention provides a method for treating a disease or condition in a subject, the method comprising co-administering to a subject in need thereof a therapeutically effective amount of at least one ULK1-inhibiting pyrimidine, and a therapeutically effective amount of an mTOR inhibitor.
Type:
Grant
Filed:
April 19, 2019
Date of Patent:
September 15, 2020
Assignees:
SALK INSTITUTE FOR BIOLOGICAL STUDIES, SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE, YALE UNIVERSITY
Inventors:
Reuben J. Shaw, Daniel F. Egan, Nicholas Cosford, Benjamin Turk, Mitchell Vamos, Dhanya Raveendra Panickar, Matthew Chun, Douglas Sheffler
Abstract: The present invention relates to methods for producing polyketide synthase variants, and for altering the activity and/or substrate specificity of putative native and variant polyketide synthases. The present invention further relates to compositions comprising said polyketide synthase variants, compounds prepared using said polyketide synthase variants, and uses of said polyketide synthase variants. In one embodiment, said polyketide synthase variant is 2-pyrone synthase.
Type:
Grant
Filed:
March 5, 2015
Date of Patent:
August 18, 2020
Assignees:
SALK INSTITUTE FOR BIOLOGICAL STUDIES, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Joseph Noel, Kate Woods, Marianne Bowman, Gordon Louie, Nancy Anderson Da Silva, Javier Pascual Cardenas
Abstract: The finding that phosphatidylserine (PtdSer) exposure on the outer leaflet of virally transduced cells triggers their engulfment by resident immune cells is described. It is demonstrated that inhibition of phospholipid scramblase 1 (PLSCR1) activity prevents PtdSer externalization and enables prolonged protection of vector-transduced cells from phagocytosis. Methods of inhibiting a virus vector-induced inflammatory response in tissue, methods of prolonging virus vector encoded transgene expression, and methods of modulating an inflammatory response in tissue of a subject, by administering an inhibitor of PLSCR1 are described.