Provided are compositions and methods useful for duplicating/amplifying a target fragment on a target DNA sequence such as a genome sequence. The editing system employs a pair of pegRNA which, by virtue of their targeting sites flanking the target fragment, extend the target fragment with reverse transcriptase (RT) templates included in the pegRNA. As the two RT templates at least include portions that are complementary to each other, they can form a duplex region which can then serve as starting point for DNA polymerase to synthesize a new strand for each strand of the target fragment, thereby duplicating the target fragment. Continue this process introduce amplification of this targeted sequence. Alternatively, this process can be done by combination of pegRNA/sgRNA or sgRNA/sgRNA. In the case of sgRNA/sgRNA in a PAM-out position, the RT enzyme and templates are not required.

This disclosure provides compositions and methods for the editing of a SERPINA1 gene with prime editing.

Provided are new Cas proteins capable of gene editing with relaxed PAM requirement, or even does not require a PAM when targeting a negatively supercoiled double stranded DNA. It is further discovered that negatively supercoiled double stranded DNA in general reduces or even eliminates the PAM requirements for all Cas proteins. Accordingly, provided are compositions and methods for conducting gene editing, including base editing and prime editing, with relaxed or no PAM requirements.

The present invention relates to LCA10 treatment using a CRISPR/Cas12f1(Cas14a1) system. In particular, the present invention relates to a composition comprising a CRISPR/Cas12f1(Cas14a1) system for LCA10 treatment, and to a treatment method using same. In addition, the present invention relates to a composition comprising a CRISPR/Cas12f1(Cas14a1) system for artificially manipulating the CEP290 gene, and to a method of editing the CEP290 gene.

The disclosure provides for compositions, systems, and methods for long-range targeted mutagenesis. In particular, the disclosure provides engineered compositions comprising a programmable nickase configured to introduce a single-strand nick in double-stranded DNA (dsDNA) at one or more targeted nick sites; a helicase configured to unwind a portion of the dsDNA at the one or more targeted nick sites; and a deaminase configured to introduce one or more base edits within the portion of unwound dsDNA. Also provided are vector and delivery systems comprising one or more polynucleotides encoding the components of the compositions, as well as modified cells, cell populations, animal models, pharmaceutical compositions, and kits comprising the compositions.

Methods and compositions for genetically modifying a cell are provided.

Provided herein are methods for treatment and uses involving dosing of compositions containing NK cells deficient in expression of FcR chain (g-NK cells) engineered with a recombinant chimeric antigen receptor (CAR) in combination with a monoclonal antibody. Among the provided methods and uses are methods and uses for treating cancer, such as multiple myeloma or lymphoma.

Provided herein are compositions and methods related split prime editors.

This invention relates to methods for producing immune cells expressing a therapeutic antigen receptor. An immune cell is provided that comprises a heterologous expression cassette. The heterologous expression cassette comprises (a) a coding sequence for a production TCR, (b) a constitutive promoter operably linked to the coding sequence, (c) a 5 targeting site, and optionally (d) a 3 targeting site. An expression construct is then introduced into the immune cell at the site of the heterologous expression cassette. The expression construct comprises a coding sequence for a therapeutic antigen receptor and the therapeutic antigen receptor is then expressed in the immune cell. Methods, reagents for use in the methods and immune cells produced by the methods are provided.

Embodiments of the instant disclosure relate to novel gene editing vectors, compositions, and methods for editing a G6PC gene to treat glucose storage diseases (e.g., GSD Ia). In certain embodiments, vectors described herein comprise one or more CRISPR/Cas9 components to allow for integration of a G6PC transgene into a target gene locus in a subject in need thereof, thereby allowing for stable expression of a therapeutic protein (e.g., glucose-6-phosphatase) and reversal and/or treatment of disease symptoms in the subject.