Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Suzanne Hartford

Brian Zambrowicz

Guochun Gong

Charleen Hunt

Andrew J Murphy

David Frendewey

Jesper Gromada

Aris I Baras

Alan R Shuldiner

Xiping Cheng

Frederick E Dewey

Noura S Abul-Husn

Yurong Xin

Omri Gottesman

Alexander Li

Daisuke Kajimura

Evangelos Pefanis

Meghan Drummond Samuelson

Susannah Brydges

Jeffery Haines

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.

Non-human animals comprising a humanized TTR locus and methods of use

Methods and compositions are provided herein for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.

Cas-ready mouse embryonic stem cells and mice and uses thereof

Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.

Transcription modulation in animals using CRISPR/Cas systems

Provided are compositions related to HSD17B13 variants, including isolated nucleic acids and proteins related to variants of HSD17B13, and cells comprising those nucleic acids and proteins. Also provided are methods related to HSD17B13 variants. Such methods include methods for modifying a cell through use of any combination of nuclease agents, exogenous donor sequences, transcriptional activators, transcriptional repressors, and expression vectors for expressing a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein. Also provided are therapeutic and prophylactic methods for treating a subject having or at risk of developing chronic liver disease.

HSD17B13 variants and uses thereof

Methods and compositions are provided for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. The methods and compositions employ non-human animals comprising a CRISPR reporter such as a genomically integrated CRISPR reporter for detecting and measuring targeted excision of a sequence between two CRISPR/Cas nuclease cleavage sites or disruption of a sequence near a CRISPR/Cas nuclease cleavage site and/or measuring CRISPR/Cas-induced recombination of the CRISPR reporter with an exogenous donor nucleic acid to convert the coding sequence for a first reporter protein to the coding sequence for a different second reporter protein. Methods and compositions are also provided for making and using these non-human animals.

Methods and compositions for assessing CRISPER/Cas-mediated disruption or excision and CRISPR/Cas-induced recombination with an exogenous donor nucleic acid in vivo

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Putnam Valley, NY, United States of America

Suzanne Hartford