Abstract: Provided herein are mice that are heterozygous knock outs for Ctla4 and homozygous knockouts for Pdcd1 (Ctla4+/? Pdcd1?/? mice), which may suffer from autoimmunity, including myocarditis and insulin-dependent diabetes mellitus. Also provided are methods of using such mice to screen for therapeutic agents that mitigate immune-related adverse events.

Abstract: Methods and compositions related to intracellular delivery of gene editing proteins are provided. The invention relates to compositions and methods for transporting gene editing polypeptides, such as Cas9 or Cas12, into a cell ex vivo or in vivo. The invention includes a targeted active gene editing (TAGE) agent that includes an extracellular cell membrane binding moiety, e.g., an antigen binding polypeptide, a cell penetrating peptide (CPP), a ligand, or combinations thereof, that specifically binds to an extracellular cell membrane-bound molecule (e.g., a cell surface molecule), and a site-directed modifying polypeptide that recognizes a nucleic acid sequence. The extracellular cell membrane binding moiety (e.g.