公开(公告)号：US20220238182A1

公开(公告)日：2022-07-28

申请号：US16772747

申请日：2018-12-15

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc. ,  President and Fellows of Harvard College

发明人： Max Walt Shen ,  Jonathan Yee-Ting Flsu ,  Mandana Arbab ,  David K. Gifford ,  David R. Liu ,  Richard Irving Sherwood

IPC分类号： G16B20/30 ,  C12N15/10 ,  G16B40/20 ,  C12N9/22 ,  C12N15/11 ,  A61K38/46 ,  A61K31/7088

摘要： The specification provides methods for introducing a desired genetic change in a nucleotide sequence using a double-strand break (DSB)-inducing genome editing system, the method comprising: identifying one or more available cut sites in a nucleotide sequence; analyzing the nucleotide sequence and available cut sites with a computational model to identify the optimal cut site for introducing the desired genetic change into the nucleotide sequence; and contacting the nucleotide sequence with a DSB-inducing genome editing system, thereby introducing the desired genetic change in the nucleotide sequence at the cut site.

公开(公告)号：US20230123669A1

公开(公告)日：2023-04-20

申请号：US17797697

申请日：2021-02-05

申请人： The Broad Institute, Inc. ,  President and Fellows of Harvard College ,  Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc.

发明人： David R. Liu ,  Mandana Arbab ,  Max Walt Shen ,  Christopher Cassa

IPC分类号： G16B40/00 ,  G16B20/50 ,  C12N15/11

摘要： The present disclosure provides a novel machine learning model capable of assisting those of ordinary skill in the art to conduct base editing by, inter alia, facilitating the selection of an appropriate guide RNA and base editor combination which are capable of conducting base editing at a certain level of efficiency and specificity on a given input target DNA sequence desired to be edited to produce an outcome genotype of interest. The disclosure also provides base editors (e.g., ABEs and CBEs), napDNAbps, cytidine deaminases, adenosine deaminases, nucleic acid sequences encoding base editors and components thereof, vectors, and cells. In addition, the disclosure provides methods of making biological or experimental training and/or validation data for training and/or validating the machine learning computational models, as well as, vectors, libraries, and nucleic acid sequences for use in obtaining said experimental training and/or validation data.

公开(公告)号：US20240287487A1

公开(公告)日：2024-08-29

申请号：US18568796

申请日：2022-06-10

申请人： The Broad Institute, Inc. ,  President and Fellows of Harvard College ,  The Regents of the University of California ,  Massachusetts Institute of Technology

发明人： Luke W. Koblan ,  David R. Liu ,  Mandana Arbab ,  Max Walt Shen ,  Andrew Vito Anzalone ,  Jeffrey Hussmann

IPC分类号： C12N9/22 ,  A61K38/00 ,  C07K14/35 ,  C12N9/10 ,  C12N9/12 ,  C12N9/78 ,  C12N15/11 ,  C12N15/90

CPC分类号： C12N9/22 ,  C07K14/35 ,  C12N9/104 ,  C12N9/1252 ,  C12N9/78 ,  C12N15/11 ,  C12N15/907 ,  C12Y207/07007 ,  C12Y305/04005 ,  A61K38/00 ,  C07K2319/00 ,  C12N2310/20 ,  C12N2800/80

摘要： Aspects of this disclosure provide compositions, strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. Fusion proteins capable of inducing a cytosine (C) to guanine (G) change (i.e., transversion changes) in a nucleic acid (e.g., genomic DNA) are provided. Fusion proteins of a nucleic acid programmable DNA binding protein (e.g., Cas9) and nucleic acid editing proteins or protein domains, e.g., deaminase domains, polymerase domains, base excision enzymes, and/or DNA repair proteins, are also provided. Methods for targeted nucleic acid editing are also provided. Reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a nucleic acid programmable DNA binding protein (e.g., Cas9), and nucleic acid editing proteins or domains, are further provided in the present disclosure.

公开(公告)号：US20190002920A1

公开(公告)日：2019-01-03

申请号：US15569232

申请日：2016-04-28

申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

发明人： Richard Sherwood ,  Mandana Arbab

IPC分类号： C12N15/90 ,  C12N15/11 ,  C12N9/22 ,  C12N15/10

摘要： The methods and compositions provided herein improve upon the methods presently used for targeted genomic modification, in part, by removing the requirement for sub-cloning of a sequence complementary to a site selected for genomic modification. The methods and compositions provided herein can be used in place of a standard CRISPR/Cas system to provide simple, fast, and inexpensive targeted modification of a genome. The methods and compositions provided herein can also be used in high-throughput genome editing applications.