公开(公告)号：WO2023060088A1

公开(公告)日：2023-04-13

申请号：PCT/US2022/077544

申请日：2022-10-04

Applicant: POSEIDA THERAPEUTICS, INC.

Inventor： LUCAS, Joseph S. ,  MADISON, Blair B.

IPC: C12N15/63 ,  C12N15/1058 ,  C12N15/85 ,  C12N15/90 ,  C12N2800/90 ,  C12N9/22 ,  C40B40/06

Abstract: This disclosure provides compositions and methods of improved transposition for use in gene therapy. Disclosed are transposon compositions which comprise non-naturally occurring structural improvements of the inverted terminal repeat (ITR) regions, in order to improve the efficacy of transposition. Disclosed are polynucleotides encoding a transposon comprising a first inverted terminal repeat (ITR) and a second ITR, wherein the first ITR and/or the second ITR comprise at least one nucleic acid substitution which confers an increase in transposition activity. Also disclosed are methods of making and methods of using these transposon compositions and polynucleotides.

公开(公告)号：WO2023010050A1

公开(公告)日：2023-02-02

申请号：PCT/US2022/074208

申请日：2022-07-27

Applicant: THE BROAD INSTITUTE, INC. ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： LIU, David, R. ,  WANG, Tina ,  MORRISON, Mary, S.

IPC: C12N15/10 ,  C12N15/1024 ,  C12N15/1037 ,  C12N15/1058

Abstract: Aspects of the disclosure relate to compositions, systems, and methods for evolving nucleic acids and proteins utilizing continuous directed evolution in the periplasm of a host cell. In some embodiments, the methods comprise passing a nucleic acid from cell-to-cell in a desired, function dependent manner. The linkage of the desired function and passage of the nucleic acid from cell-to-cell allows for continuous selection and mutation of the nucleic acid.

公开(公告)号：WO2023057688A1

公开(公告)日：2023-04-13

申请号：PCT/FI2022/050664

申请日：2022-10-05

Applicant: TURUN YLIOPISTO

Inventor： METSÄ-KETELÄ, Mikko ,  BARAL, Bikash ,  AKHGARINAZARLOU, Amirbehzad

IPC: C12N15/10 ,  C12N15/76 ,  C12N15/74 ,  C12N15/1058 ,  C12N15/70

Abstract: The invention relates to a method for metabolic engineering of Actinomycetes. The method is based on traditional mutagenesis combined with reporter-guided single cell technologies. The method may be used for various purposes, such as for producing or increasing yields of endogenous target proteins or secondary metabolites, for replacing medium optimization in the production of target proteins or secondary metabolites, and for activating silent target genes or silent biosynthetic gene cluster. Also provided are metabolically engineered Actinomycetes strains obtainable by the method.

公开(公告)号：WO2021138560A2

公开(公告)日：2021-07-08

申请号：PCT/US2020/067666

申请日：2020-12-31

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

Inventor： WANG, Harris He

IPC: C12N15/63 ,  C12N15/90 ,  C12N9/22 ,  C07K2319/00 ,  C12N15/1058 ,  C12N15/1093 ,  C12N15/113 ,  C12N15/70 ,  C12N15/74 ,  C12N2310/20 ,  C12N2310/3517 ,  C40B40/08

Abstract: The present invention relates to components, systems, and methods transcriptional modification (e.g., transcriptional activation) or methods of identifying transcriptional effectors based on Cas9-transcription effector fusion protein and gRNA sequence targeting.

公开(公告)号：WO2021202651A1

公开(公告)日：2021-10-07

申请号：PCT/US2021/025072

申请日：2021-03-31

Applicant: VOYAGER THERAPEUTICS, INC.

Inventor： NONNENMACHER, Mathieu E. ,  HOU, Jinzhao ,  WANG, Wei ,  CHILD, Matthew

IPC: C07K14/005 ,  C12N15/10 ,  C12N15/86 ,  C40B30/06 ,  C12N15/1058 ,  C12N15/1096 ,  C12N2750/14122 ,  C12N2750/14143 ,  C40B40/08 ,  C40B50/06

Abstract: The disclosure relates to compositions, methods, and processes for the preparation, use, and/or formulation of adeno-associated virus capsid proteins, wherein the capsid proteins comprise targeting peptide inserts for enhanced tropism to a target tissue.

公开(公告)号：WO2021151065A2

公开(公告)日：2021-07-29

申请号：PCT/US2021/014887

申请日：2021-01-25

Applicant: THE GENERAL HOSPITAL CORPORATION

Inventor： KLEINSTIVER, Benjamin ,  WALTON, Russell T.

IPC: C40B40/06 ,  A61K38/46 ,  G01N33/00 ,  G01N33/533 ,  C12P21/04 ,  C12N5/071 ,  C12N15/00 ,  C07H21/04 ,  C12N15/1058 ,  C12N15/1093 ,  C12N2310/20

Abstract: The disclosure provides methods for the concurrent assessment of large numbers of genome engineering proteins, including CRISPR nucleases and base editors. Specifically, the disclosure provides methods of providing a plurality of individual discrete samples comprising populations of cells, wherein each population of cells overexpresses both (i) a single genome engineering protein or a variant thereof and (ii) a reporter protein, lysing the cells to release the proteins; normalizing levels of the genome engineering proteins or variants thereof; allowing the genome engineering proteins or variants thereof to combine with a guide RNA under conditions sufficient to form ribonucleoprotein complexes in each sample; contacting each sample with a plurality of analysis substrates, determining levels of each of the analysis substrate in each sample at a plurality of times; and calculating rate of depletion or enrichment of each of the analysis substrates from each sample.

公开(公告)号：WO2021119261A1

公开(公告)日：2021-06-17

申请号：PCT/US2020/064224

申请日：2020-12-10

Applicant: HOMODEUS, INC.

Inventor： ROTHBERG, Jonathan, M. ,  ZHANG, Zhizhuo ,  GLANTZ, Spencer

IPC: G16B20/50 ,  G16B40/00 ,  G06N20/10 ,  G16B30/00 ,  G16B50/10 ,  C12N15/1058 ,  C12N15/1089 ,  G16B35/10

Abstract: The present disclosure provides, in some embodiments, techniques for using generative machine learning models to generate new functional protein sequences based on an input protein structure, such that the new functional protein sequences are structurally similar to the input protein structure but have new and diverse protein sequences. The techniques described herein may be used alone, or in conjunction with structural prediction algorithms and/or to generate diversified gene libraries in directed evolution techniques.

公开(公告)号：WO2023288304A8

公开(公告)日：2023-01-19

申请号：PCT/US2022/073781

申请日：2022-07-15

Applicant: THE BROAD INSTITUTE, INC. ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： LIU, David, R. ,  ZHAO, Kevin, Tianmeng

IPC: C12N9/12 ,  A61P7/00 ,  C12N9/22 ,  C12N9/78 ,  C12N15/10 ,  C07K2319/09 ,  C07K2319/80 ,  C07K2319/92 ,  C12N15/102 ,  C12N15/1058 ,  C12N15/70 ,  C12N2310/20 ,  C12Y305/04004

Abstract: The present disclosure provides adenine base editors (ABEs) that have context specificity, i.e., a preference for a pyrimidine positioned 5' of the target adenosine, or preference for a purine positioned 5' of the target adenosine. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising the ABEs. Also provided are vectors useful for the generation and delivery of the ABEs, including vector systems for engineering the ABEs through directed evolution. Cells containing such vectors and ABEs are also provided. Further provided are methods of treatment and uses comprising administering the ABEs.

公开(公告)号：WO2022226423A2

公开(公告)日：2022-10-27

申请号：PCT/US2022/026223

申请日：2022-04-25

Applicant: THE J. DAVID GLADSTONE INSTITUTES, A TESTAMENTARY TRUST ESTABLISHED UNDER THE WILL OF J. DAVID GLADSTONE ,  RODICK, Robert

Inventor： WEINBERGER, Leor S. ,  CHATURVEDI, Sonali

IPC: A61P31/14 ,  C07K14/005 ,  C12N15/11 ,  C12N15/1058 ,  C12N15/1065 ,  C12N15/1131 ,  C12N15/86 ,  C12N2310/11 ,  C12N2770/20021 ,  C12N2770/20022 ,  C12N2770/20032 ,  C12N7/00 ,  C40B40/02

Abstract: Described herein are compositions of recombinant SARS-CoV-2 constructs and particles that can interfere with or block infection of uninfected cells. The compositions and methods described herein are useful for treatment of SARS-Co V-2 infections. The recombinant SARS-CoV-2 construct cannot replicate by itself, but can replicate in the presence of infective SARS-CoV-2 (e.g., replication competent SARS-CoV-2). Thus, the present application in one aspect provides a recombinant SARS-Co V-2 construct (e.g., SARS-CoV-2 TIP) capable of interfering with SARS-CoV-2 replication, wherein the recombinant SARS-CoV-2 construct cannot replicate by itself, and wherein the recombinant SARS-CoV-2 construct can replicate in the presence of SARS-CoV-2.

公开(公告)号：WO2022115595A8

公开(公告)日：2022-06-02

申请号：PCT/US2021/060808

申请日：2021-11-24

Applicant: THE UNIVERSITY OF CHICAGO

Inventor： MOELLERING, Raymond E. ,  SPELTZ, Thomas E. ,  SHANGGUAN, Sean

IPC: A61K38/00 ,  C07K14/435 ,  C07K19/00 ,  C12N15/62 ,  A61P35/00 ,  C07K14/4702 ,  C07K2319/71 ,  C12N15/1058 ,  C12N15/63

Abstract: In aspects, the invention provides a polypeptide construct comprising (a) a first polypeptide comprising an amino acid sequence derived from a basic helix of a transcription factor protein that comprises a basic helix-loop-helix domain; and (b) a second polypeptide comprising an amino acid sequence derived from a helix that extends in the C-terminal direction from the end of the loop of a basic helix-loop-helix domain of a transcription factor protein that comprises a basic helix-loop-helix domain; wherein the first polypeptide and the second polypeptide are linked through an interpolypeptide covalent linkage. Additional aspects of the invention are as described herein.