Abstract: The present disclosure provides automated modules and instruments for improved detection of nuclease genome editing of live cells. The disclosure provides improved modules—including high throughput modules—for screening cells that have been subjected to editing and identifying and selecting cells that have been properly edited.
Type:
Grant
Filed:
April 30, 2022
Date of Patent:
June 27, 2023
Assignee:
INSCRIPTA, INC.
Inventors:
Andrew Garst, Richard Fox, Eileen Spindler, Amy Hiddessen, Phillip Belgrader, Don Masquelier, Bruce Chabansky, Michael Graige
Abstract: The present disclosure provides compositions of matter, methods, modules and automated multi-module instrumentation for performing editing of live cells followed by curing of editing and engine vectors from prior rounds of editing, followed by curing of the curing vector.
Type:
Application
Filed:
February 9, 2023
Publication date:
June 15, 2023
Applicant:
Inscripta, Inc.
Inventors:
Tian TIAN, Eileen SPINDLER, Clint DAVIS, Charles JOHNSON, Andrew GARST
Abstract: The present disclosure relates to automated multi-module instruments, compositions and methods for performing nucleic acid-guided nuclease editing; specifically, the disclosure provides nucleic acid cassettes, plasmids, vectors, and compositions comprising the same that employ homologous recombination for genome engineering by having a CRISPR nuclease cause a specific DSB while tethered to a repair nucleic acid.
Abstract: The present disclosure provides a sphere-packing lattice electroporation device configured for use as a stand-alone unit or in an automated multi-module cell processing environment and configured to decrease cell processing time and cell survival. The sphere-packing lattice utilizes lattice-forming beads that are uniform in size and that self-assemble into a crystalline-like lattice.
Abstract: The present disclosure relates to methods and compositions for nuclease-mediated plasmid integration into the genome of a population of live cells, as well as automated multi-module instruments for performing these methods and using these compositions.
Abstract: The present disclosure provides automated multi-module instrumentation and automated methods for performing recursive editing of live cells with curing of editing vectors from prior rounds of editing.
Type:
Grant
Filed:
February 20, 2022
Date of Patent:
April 25, 2023
Assignee:
Inscripta, Inc.
Inventors:
Charles Johnson, Tian Tian, Eileen Spindler
Abstract: The present disclosure relates to methods, compositions, and automated multi-module cell processing instruments for modulation of gene utilizing nuclease-mediated systems, and in particular, inactive (“dead”) nuclease-mediated CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) systems.
Type:
Application
Filed:
October 7, 2022
Publication date:
April 13, 2023
Applicant:
Inscripta, Inc.
Inventors:
Tian TIAN, Patrick WESTFALL, Eileen SPINDLER, Juhan KIM
Abstract: In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.
Type:
Grant
Filed:
March 11, 2022
Date of Patent:
March 7, 2023
Assignee:
Inscripta, Inc.
Inventors:
Jorge Bernate, Kevin Ness, Phillip Belgrader, Don Masquelier, Ryan Gill
Abstract: The present disclosure relates to compositions, methods, modules and automated integrated instrumentation for multiplex delivery of “landing pad” edits into the genomes of a population of live cells. The landing pads then may be leveraged to insert very large DNA sequences into the genomes of the population of live cells.
Abstract: This invention relates to compositions of matter, methods, modules and automated, end-to-end closed instruments for automated mammalian cell growth, reagent bundle creation and mammalian cell transfection followed by nucleic acid-guided nuclease editing in live mammalian cells. The disclosed compositions and method entail making “reagent bundles” comprising many (hundreds of thousands to millions) clonal copies of an editing cassette and delivering or co-localizing the reagent bundles with live mammalian cells such that the editing cassettes edit the cells and the edited cells continue to grow.
Type:
Grant
Filed:
April 23, 2021
Date of Patent:
February 28, 2023
Assignee:
Inscripta, Inc.
Inventors:
Phillip Belgrader, Nathan Bade, Christian Siltanen, Aamir Mir, Xi-Jun Chen, Janine Mok, Burak Dura, Bruce Chabansky, David Stumbo, Eric Smith, Jorge Bernate
Abstract: Provided herein are methods and composition for trackable genetic variant libraries. Further provided herein are methods and compositions for recursive engineering. Further provided herein are methods and compositions for multiplex engineering. Further provided herein are methods and compositions for enriching for editing and trackable engineered sequences and cells using nucleic acid-guided nucleases.
Type:
Grant
Filed:
March 7, 2019
Date of Patent:
February 21, 2023
Assignees:
THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE, INSCRIPTA, INC.
Inventors:
Ryan T. Gill, Andrew Garst, Tanya Elizabeth Warnecke Lipscomb, Marcelo Colika Bassalo, Ramsey Ibrahim Zeitoun
Abstract: Disclosed systems and methods relate to predicting the relative representation of genomic variants in an edited cell population, based on the editing cassette design representation in an editing cassette design library used to generate the edited cell population. A library of editing cassette designs is generated, and a feature vector, or sequence embedding, is developed for each design using natural language processing techniques. The feature vector may be based upon sequence attributes and editing kinetics of each cassette design as well as attributes that describe the library context. Features may include sequence embeddings generated from a neural network, linguistic-type distances, and statistical distance summaries thereof. The feature vectors are classified using one or more machine learning models, and the classified feature vectors are used to predict the representation of each design an edited cell population.
Type:
Grant
Filed:
October 1, 2021
Date of Patent:
January 31, 2023
Assignee:
Inscripta, Inc.
Inventors:
Andrea Halweg-Edwards, Thomas Hraha, Krishna Yerramsetty, Shea Lambert, Miles Gander, Matthew David Estes, Chad Douglas Sanada, Isaac David Wagner, Paul Hardenbol
Abstract: The present disclosure methods for identifying binding partners using cell surface display libraries, where the cells of the library display engineered peptides on their cell surfaces for identification of peptides that bind to targets of interest. The engineered peptides are preferably expressed in the cells under conditions that provide both secretion and display of the engineered peptides on the cell surfaces, thus providing access of the engineered peptides to identify potential binding pairs. The cell libraries cab be engineered using an automated editing system that provides for one or more targeted edits per cell.
Type:
Grant
Filed:
August 9, 2020
Date of Patent:
January 17, 2023
Assignee:
Inscripta, Inc.
Inventors:
Stephen Federowicz, Deanna Church, Michael Graige
Abstract: The present disclosure provides shuttle vectors for editing exogenous polynucleotides in heterologous live cells, as well as automated methods, modules, and multi-module cell editing instruments and systems for performing the editing methods.
Abstract: The present disclosure provides compositions and methods to increase the percentage of edited cells in a cell population when employing nucleic-acid guided editing, as well as automated multi-module instruments for performing these methods. Specifically, the disclosure relates to methods, compositions, modules and automated multi-module cell processing instruments that increase the efficiency of nucleic acid-guided editing in a cell population using a nucleic acid nuclease (i.e., an RNA-guided nuclease or “RGN”)/single-strand binding protein (“SSB”) fusion system. The system leverages a single-strand binding protein (SSP) and single-strand DNA annealing protein (“SSAP”) interactions to drive enhanced recruitment.
Abstract: The present disclosure provides instrumentation and automated methods for creating cell surface display libraries, where the cells of the library display engineered peptides on their cell surfaces for identification of antigens that bind to T-cell receptors. The engineered peptides may be putative antigens or binding regions of the T-cell receptors.
Type:
Grant
Filed:
April 25, 2022
Date of Patent:
October 18, 2022
Assignee:
Inscripta, Inc.
Inventors:
Stephen Federowicz, Deanna Church, Michael Graige
Abstract: This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells. The present compositions and methods entail viral delivery of an editing cassette to live mammalian cells such that the editing cassettes edit the cells and the edited cells continue to grow, preferably using a fully-automated end-to-end instrument to process the cells without human intervention to enhance cell processing uniformity and to maintain the integrity of the cell culture.
Type:
Grant
Filed:
January 25, 2022
Date of Patent:
August 9, 2022
Assignee:
Inscripta, Inc.
Inventors:
Phillip Belgrader, Christian Siltanen, William Watterson, Burak Dura, Bruce Chabansky, David Stumbo, Eric Smith, Jorge Bernate
Abstract: Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.
Type:
Grant
Filed:
January 29, 2022
Date of Patent:
August 9, 2022
Assignee:
Inscripta, Inc.
Inventors:
Andrew Garst, Ryan T. Gill, Tanya Elizabeth Warnecke Lipscomb
Abstract: The present disclosure provides instrumentation and automated methods for creating cell surface display libraries, where the cells of the library display engineered peptides on their cell surfaces for identification of antigens that bind to T-cell receptors. The engineered peptides may be putative antigens or binding regions of the T-cell receptors.
Type:
Grant
Filed:
March 9, 2022
Date of Patent:
July 26, 2022
Assignee:
Inscripta, Inc.
Inventors:
Stephen Federowicz, Deanna Church, Michael Graige
Abstract: The present disclosure provides automated modules and instruments for improved detection of nuclease genome editing of live cells. The disclosure provides improved modules—including high throughput modules—for screening cells that have been subjected to editing and identifying and selecting cells that have been properly edited.
Type:
Grant
Filed:
February 21, 2022
Date of Patent:
June 21, 2022
Assignee:
Inscripta, Inc.
Inventors:
Eileen Spindler, Amy Hiddessen, Andrew Garst, Michael Graige, Richard Fox, Phillip Belgrader, Don Masquelier, Bruce Chabansky