A non-naturally occurring or engineered composition comprising: a delivery system operably configured to deliver CRISPR-Cas complex components or polynucleotide sequences comprising or encoding said components into a eukaryotic cell, wherein said CRISPR-Cas complex is operable in the eukaryotic cell; I. one or more CRISPR-Cas complex polynucleotide sequences comprising or encoding for expression in the eukaryotic cell: (a) a guide sequence capable of hybridizing to a target sequence in a eukaryotic cell, (b) a tracr mate sequence, and (c) a tracr sequence, and II. a CRISPR enzyme comprising one or more heterologous functional domains or a polynucleotide encoding a CRISPR enzyme comprising one or more heterologous functional domains for expression in the eukaryotic cell; wherein: the tracr mate sequence hybridizes to the tracr sequence, the guide sequence directs sequence-specific binding of a CRISPR complex to the target sequence, the CRISPR complex comprises the CRISPR enzyme complexed with the guide sequence that is hybridized to the target sequence, and the tracr mate sequence that is hybridized to the tracr sequence, the CRISPR enzyme comprises one or more mutations, such that the enzyme has altered nuclease activity compared with the wild type enzyme, wherein the one or more heterologous functional domains comprises at least one or more Nuclear Localization Signals NLS(s). a delivery system operably configured to deliver CRISPR-Cas complex components or polynucleotide sequences comprising or encoding said components into a eukaryotic cell, wherein said CRISPR-Cas complex is operable in the eukaryotic cell; I. one or more CRISPR-Cas complex polynucleotide sequences comprising or encoding for expression in the eukaryotic cell: (a) a guide sequence capable of hybridizing to a target sequence in a eukaryotic cell, (b) a tracr mate sequence, and (c) a tracr sequence, and II. a CRISPR enzyme comprising one or more heterologous functional domains or a polynucleotide encoding a CRISPR enzyme comprising one or more heterologous functional domains for expression in the eukaryotic cell; I. one or more CRISPR-Cas complex polynucleotide sequences comprising or encoding for expression in the eukaryotic cell: (a) a guide sequence capable of hybridizing to a target sequence in a eukaryotic cell, (b) a tracr mate sequence, and (c) a tracr sequence, and (a) a guide sequence capable of hybridizing to a target sequence in a eukaryotic cell, (b) a tracr mate sequence, and (c) a tracr sequence, and II. a CRISPR enzyme comprising one or more heterologous functional domains or a polynucleotide encoding a CRISPR enzyme comprising one or more heterologous functional domains for expression in the eukaryotic cell; the tracr mate sequence hybridizes to the tracr sequence, the guide sequence directs sequence-specific binding of a CRISPR complex to the target sequence, the CRISPR complex comprises the CRISPR enzyme complexed with the guide sequence that is hybridized to the target sequence, and the tracr mate sequence that is hybridized to the tracr sequence, the CRISPR enzyme comprises one or more mutations, such that the enzyme has altered nuclease activity compared with the wild type enzyme, wherein the one or more heterologous functional domains comprises at least one or more Nuclear Localization Signals NLS(s).