A non-naturally occurring or engineered "Clustered Regularly Interspersed Short Palindromic Repeat (CRISPR)-CRISPR associated (Cas) "system (CRISPR system) targeting one genomic target sequence in a target cell, the system comprising a viral expression vector which comprises: 1) a nucleotide sequence encoding an endonuclease enzyme capable of generating cohesive ends, said nucleotide sequence being operably linked to one or more regulatory sequences located on the vector; 2) a nucleotide sequence encoding a protein capable of promoting cell death, said nucleotide sequence not being operably linked to any regulatory sequence located on the vector; 3) a first target nucleotide sequence and a second target nucleotide sequence located, respectively, downstream of the 3' end and upstream of the 5' end of the nucleotide sequence encoding the protein capable of promoting cell death, both the first target nucleotide sequence and the second target nucleotide sequence being located downstream of the 3' end of a Protospacer Adjacent Motif nucleotide sequence; 4) a nucleotide sequence encoding a first guide RNA (first gRNA) operably linked to one or more regulatory sequences located on the vector, wherein said first gRNA comprises a first scaffold nucleotide sequence capable of binding the endonuclease enzyme and a first guide nucleotide sequence capable of hybridizing to the first target nucleotide sequence; and 5) a nucleotide sequence encoding a second guide RNA (second gRNA) operably linked to one or more regulatory sequences located on the viral expression vector, wherein said second gRNA comprises a second scaffold nucleotide sequence capable of binding the endonuclease enzyme and a second guide nucleotide sequence capable of hybridizing to the second target nucleotide sequence, wherein the first target nucleotide sequence corresponds to the genomic target sequence in the target cell targeted by the CRISPR system; wherein the first target nucleotide sequence and the second target nucleotide sequence are different, and wherein the first target nucleotide sequence and the second target nucleotide sequence are selected so that the protruding single-stranded portions of the respective cohesive ends generated upon endonuclease enzyme cleavage are complementary sequences; and wherein the genomic target sequence in the target cell targeted by the CRISPR system comprises at least one nonsense gene mutation. 1) a nucleotide sequence encoding an endonuclease enzyme capable of generating cohesive ends, said nucleotide sequence being operably linked to one or more regulatory sequences located on the vector; 2) a nucleotide sequence encoding a protein capable of promoting cell death, said nucleotide sequence not being operably linked to any regulatory sequence located on the vector; 3) a first target nucleotide sequence and a second target nucleotide sequence located, respectively, downstream of the 3' end and upstream of the 5' end of the nucleotide sequence encoding the protein capable of promoting cell death, both the first target nucleotide sequence and the second target nucleotide sequence being located downstream of the 3' end of a Protospacer Adjacent Motif nucleotide sequence; 4) a nucleotide sequence encoding a first guide RNA (first gRNA) operably linked to one or more regulatory sequences located on the vector, wherein said first gRNA comprises a first scaffold nucleotide sequence capable of binding the endonuclease enzyme and a first guide nucleotide sequence capable of hybridizing to the first target nucleotide sequence; and 5) a nucleotide sequence encoding a second guide RNA (second gRNA) operably linked to one or more regulatory sequences located on the viral expression vector, wherein said second gRNA comprises a second scaffold nucleotide sequence capable of binding the endonuclease enzyme and a second guide nucleotide sequence capable of hybridizing to the second target nucleotide sequence, wherein the first target nucleotide sequence corresponds to the genomic target sequence in the target cell targeted by the CRISPR system; wherein the first target nucleotide sequence and the second target nucleotide sequence are different, and wherein the first target nucleotide sequence and the second target nucleotide sequence are selected so that the protruding single-stranded portions of the respective cohesive ends generated upon endonuclease enzyme cleavage are complementary sequences; and wherein the genomic target sequence in the target cell targeted by the CRISPR system comprises at least one nonsense gene mutation.