Abstract: The present disclosure provides a system for editing genomic DNA, the system comprising an asymmetric donor DNA template; and methods of editing genomic DNA involving use of an asymmetric donor DNA template. The present disclosure provides a system for editing genomic DNA, the system comprising a Cas9 polypeptide with reduced enzymatic activity; and methods of editing genomic DNA involving use of a Cas9 polypeptide with reduced enzymatic activity.

Abstract: Methods of modulating the activity of a cyclic dinucleotide (CDN) in a cell via membrane transporter are provided. Aspects of the methods may include contacting a cell with a CDN transporter-modulating agent to modulate transport of a CDN into the cell. In some cases, the CDN transporter-modulating agent modulates SLC19A1-mediated transport of the CDN into the cell. Also provided are compositions and kits for use in practicing the subject methods. The methods and compositions find use in a variety of applications, including therapeutic applications, such as methods of treating cancer or an inflammatory disease.

Abstract: The present disclosure provides a system for editing genomic DNA, the system comprising an asymmetric donor DNA template; and methods of editing genomic DNA involving use of an asymmetric donor DNA template. The present disclosure provides a system for editing genomic DNA, the system comprising a Cas9 polypeptide with reduced enzymatic activity; and methods of editing genomic DNA involving use of a Cas9 polypeptide with reduced enzymatic activity.

Abstract: The present disclosure provides a method of modifying a globin gene in the genome of a hematopoietic stem/progenitor cell (HSPC), the method comprising: A) obtaining HSPCs from an individual having a globin gene comprising a sickle cell disease (SCD)-associated single nucleotide polymorphism (SNP) to generate an in vitro population of CD34+ HSPCs and B) contacting the in vitro population with a genome editing composition, as described in further detail below. Also provided is a method of treating sickle cell disease (SCD) in an individual including administering to an individual an in vitro mixed population derived from the method of modifying a globin gene, as well as kits for practicing the same.

Abstract: The present disclosure provides a system for editing genomic DNA, the system comprising an asymmetric donor DNA template; and methods of editing genomic DNA involving use of an asymmetric donor DNA template. The present disclosure provides a system for editing genomic DNA, the system comprising a Cas9 polypeptide with reduced enzymatic activity; and methods of editing genomic DNA involving use of a Cas9 polypeptide with reduced enzymatic activity.

Abstract: Provided herein are conformationally stabilized ubiquitin proteins and methods for using the same to identify agents that bind to the stabilized ubiquitin protein or that bind to a protein that interacts with or processes the stabilized form of the ubiquitin protein. Also provided herein are methods for screening for conformationally stabilized proteins having increased binding affinity to a binding partner in comparison to the binding affinity of the wildtype form of the protein to the binding partner.

Abstract: Provided herein are conformationally stabilized ubiquitin proteins and methods for using the same to identify agents that bind to the stabilized ubiquitin protein or that bind to a protein that interacts with or processes the stabilized form of the ubiquitin protein. Also provided herein are methods for screening for conformationally stabilized proteins having increased binding affinity to a binding partner in comparison to the binding affinity of the wildtype form of the protein to the binding partner.