Fecha de publicación: -- Fuente: WIPO "tomato" Aspects of the present disclosure relate to fusion polypeptides comprising a CRISPR-Cas effector polypeptide and a heterologous polypeptide (e.g., a targeting moiety, an endosomal escape peptide, and/or a pH responsive polypeptide domain). In some aspects, the present disclosure provides compositions comprising a CRISPR-Cas effector polypeptide conjugated to one or more POEGMA molecules or one or more PEG molecules; and a heterologous polypeptide. In some aspects, the present disclosure provides compositions comprising a fusion polypeptide of the present disclosure and a guide nucleic acid. In some aspects, the present disclosure also provides fusion polynucleotides (e.g., an oligonucleotide or a short interference RNA) and a heterologous polypeptide (e.g., a targeting moiety, an endosomal escape peptide, and/or a pH responsive polypeptide domain). The present disclosure provides methods of modifying a target nucleic acid in a cell, such as a eukaryotic cell.