Harvard College

Pairwise Plants Services, Inc.

The Broad Institute, Inc.

Yongjoo Kim

David R Liu

Alexis Christine Komor

Aaron Hummel

Holly A Rees

Kevin Tianmeng Zhao

Joseph Matthew Watts

Nathaniel Graham

Shai Joshua Lawit

Ming Cheng

Brian Charles Wilding Crawford

Julius Mojica

David Gerhard Schwark

Thomas J Poorten

Nicholas Bate

Sathya Sheela Jali

Doug Heckart

Qingchun Shi

Provided herein are compositions, systems, and methods for delivering an effector protein into a cell. The present disclosure, in some aspects, provide novel proteins delivering an effector protein into a cell. The novel proteins are supernegatively charged proteins derived from highly anionic proteins identified from the proteome (e.g., human proteome). The novel protein tags can be associated (e.g., covalently or nocovalently) with the protein to be delivered to facilitate delivery of the effector protein into a cell.

Supernegatively charged proteins and uses thereof

Methods and compositions for generating transgene-free plants are described. In particular, the transgene-free plants are regenerated by transient expression of morphogenic regulators in a plant cell that is precisely edited using a gene-editing methodology. Also, provided are transformed plants, plant cell, tissues, and seeds in which a target gene is edited, but non-transgenic.

Morphogenic regulators and methods of using the same

Some aspects of this disclosure provide 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. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.

Nucleobase editors and uses thereof

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids or the modification of nucleic acids or proteins, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins e.g., GeoCas9 or variants thereof, and effector domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing or protein modification are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a GeoCas9 and effector domains, are provided.

Nucleobase editors comprising GeoCas9 and uses thereof

Described herein are methods of modifying or editing a target nucleic acid such as methods that edit adenine to cytosine, thymine, or guanine. Compositions and systems for modifying or editing a target nucleic acid are also described. Methods, compositions and systems described herein may be used for generating allelic diversity.

Compositions, systems, and methods for base diversification

This invention relates to compositions and methods for modifying Homeodomain-leucine zipper (HD-Zip) transcription factors in plants to suppress shade avoidance response in plants. The invention further relates to plants produced using the methods and compositions of the invention.

Suppression of shade avoidance response in plants

Some aspects of this disclosure provide 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. In some embodiments, fusion proteins comprise a Gam protein, a napDNAbp, and a cytidine deaminase. In some embodiments, the fusion proteins further comprise a UGI domain. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a Gam protein, a cytidine deaminase and nucleic acid editing proteins or domains, are provided.

High efficiency base editors comprising Gam

This invention relates to recombinant nucleic constructs comprising Type V CRISPR-Cas effector proteins, reverse transcriptases and extended guide nucleic acids and methods of use thereof for modifying nucleic acids in plants.

Compositions and methods for RNA-encoded DNA-replacement of alleles

This invention relates to CRISPR-Cas nucleases codon optimized for expression in plants and nucleic acid constructs encoding base editors comprising a CRISPR-Cas nuclease and a deaminase domain, wherein the nucleic acid constructs are optimized for expression in a plant. The invention further relates to methods of modifying nucleic acids using the nucleic acid constructs.

Growing community of inventors

Cambridge, MA, United States of America

Yongjoo Kim