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:
Grant
Filed:
July 15, 2020
Date of Patent:
January 3, 2023
Assignee:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Annette Atkins, Sihao Liu, Ruth T. Yu
Abstract: Provided herein are methods and compositions for editing a target genome in a cell comprising contacting the cell with (i) a single homology arm construct comprising a replacement sequence and a targeted endonuclease cleavage site; and (ii) a targeted endonuclease, wherein the replacement sequence comprises at least one nucleotide difference compared to the target genome and wherein the target genome comprises a sequence homologous to the targeted endonuclease cleavage site.
Type:
Application
Filed:
September 20, 2019
Publication date:
October 20, 2022
Applicant:
Salk Institute for Biological Studies
Inventors:
Juan Carlos Izpisua Belmonte, Keiichiro Suzuki, Mako Tsuji, Reyna Hernandez-Benitez
Abstract: The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency.
Type:
Application
Filed:
December 8, 2020
Publication date:
October 6, 2022
Applicant:
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
RONALD EVANS, MICHAEL DOWNES, YASUYUKI KIDA, TERUHISA KAWAMURA, ZONG WEI, RUTH T. YU, ANNETTE R. ATKINS
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 1, 2020
Date of Patent:
September 13, 2022
Assignees:
The 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 features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.
Type:
Grant
Filed:
December 4, 2019
Date of Patent:
August 30, 2022
Assignee:
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
Sagar P. Bapat, Ye Zheng, Ronald Evans, Michael Downes, Annette R. Atkins, Ruth T. Yu
Abstract: Provided herein are compositions and systems for reconstitution of RNA molecules, including methods for using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a therapeutic protein, for example to treat a genetic disease or cancer.
Type:
Application
Filed:
May 10, 2022
Publication date:
August 25, 2022
Applicant:
Salk Institute for Biological Studies
Inventors:
Lukas Christoph Bachmann, Samuel Lawrence Pfaff
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:
December 16, 2019
Date of Patent:
August 23, 2022
Assignees:
The Salk Institute for Biological Studies, Mitobridge, Inc.
Inventors:
Ronald M. Evans, Michael Downes, Thomas J. Baiga, Joseph P. Noel, Emi Kanakubo Embler, Weiwei Fan, John F. W. Keana, Mark G. Bock, Authur F. Kluge, Mike A. Patane
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:
Grant
Filed:
June 30, 2020
Date of Patent:
August 2, 2022
Assignee:
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: The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.
Type:
Application
Filed:
March 28, 2022
Publication date:
July 14, 2022
Applicant:
Salk Institute for Biological Studies
Inventors:
Ronald EVANS, Michael DOWNES, Annette ATKINS, Eiji YOSHIHARA, Ruth YU
Abstract: Methods are provided for reducing blood glucose, which utilize an agent that increases the biological activity of a vitamin D receptor (VDR) (e.g., a VDR agonist), in combination with an antagonist of bromodomain-containing protein 9 (BRD9). IN some examples, such methods treat type II diabetes.
Type:
Grant
Filed:
January 8, 2020
Date of Patent:
July 5, 2022
Assignee:
Salk Institute for Biological Studies
Inventors:
Ronald M. Evans, Michael Downes, Zong Wei, Annette Atkins, Ruth T. Yu
Abstract: Provided herein are synthetic RNA molecules for reconstitution of RNA molecules, including compositions and methods of using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a therapeutic protein, for example to treat a genetic disease or cancer.
Type:
Application
Filed:
September 27, 2021
Publication date:
May 12, 2022
Applicant:
Salk Institute for Biological Studies
Inventors:
Lukas Christoph Bachmann, Samuel Lawrence Pfaff
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: 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: 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: An adenovirus comprising an E1A polypeptide comprising one or more modifications and comprising an E4orf6/7 polypeptide comprising one or more modifications is described. Compositions and kits comprising the modified adenoviruses are also described. Further described is a method of treating a proliferative disorder in a subject comprising administering to the subject an adenovirus comprising the E1A polypeptide comprising one or more modifications and comprising the E4orf6/7 polypeptide comprising one or more modifications.