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.

Methods and compositions are provided for identifying any of the presence, location and phasing of methylated and/or hydroxymethylated cytosines in nucleic acids including long stretches of DNA. In some embodiments, the method may comprise reacting a first portion (aliquot) of a nucleic acid sample with a dioxygenase and optionally a glucosyltransferase in a reaction mixture containing the nucleic acid followed by a reaction with a cytidine deaminase to detect and optionally map .sup.5mC in a DNA. Optionally, a second portion can be reacted with glucosyltransferase followed by reaction with a cytidine deaminase to detect and optionally map .sup.5hmC in a DNA.

The present invention provides a triple-mode antibody display system that simultaneously matures, displays and secretes an antibody to a target of interest. An antibody in vivo-matured and complexed with membrane anchored bait can be expressed on the surface of the host cell, while complexed with a soluble bait the antibody is secreted from the host cell. Methods of using the system for identifying binders that bind specifically to an antigen of interest are also provided. Polypeptides, polynucleotides and host cells useful for making the protein binder display system are also provided along with methods of use thereof

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.

The present disclosure provides methods for treating cancer in a subject (by inhibiting e.g., APOBEC3A, APOBEC3B, or REV1), and methods of diagnosing cancer in a subject. Methods of tracking mutagenesis induced by a gene of interest (e.g., APOBEC3A, APOBEC3B, or REV1) and methods of screening for inhibitors and synthetic lethalities are also described herein. Further provided by the present disclosure are cell lines and antibodies for use in the methods described herein.

Methods and compositions for performing highly sensitive in vitro assays to define substrate preferences and off-target sites of nucleic-acid binding, modifying, and cleaving agents.

The present disclosure provides for endonuclease enzymes having distinguishing domain features, as well as methods of using such enzymes or variants thereof.

The present invention discloses a modified Cannabis plant exhibiting herbicide resistance (HR) as compared to a Cannabis plant absent of such modification. The modified plant comprises at least one genetically modified HR-related gene comprising at least one mutation conferring herbicide resistance to the plant. The present invention further discloses methods for producing the same.

The present disclosure relates to compositions and methods 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 a plant genome. The disclosure provides base editing fusion polypeptides of a DNA binding domain, e.g., Cas9, and a cytidine deaminase domain. The base editors perform equally well or outperform existing technologies in C-to-T base editing efficiency while maintaining low frequency of introducing C-to-A and C-to-G byproducts.

This disclosure relates to modified guide RNAs having improved in vitro and in vivo activity in gene editing methods. This disclosure also relates to N. meningitidis Cas9 (NmeCas9) gene editing systems with modified guide RNAs.