non-human animal, and methods for testing and for optimizing the ability of a crispr / cas nuclease to excise a genomic nucleic acid in vivo, to test the crispr / cas-induced recombination of a genomic acid with an exogenous donor nucleic acid in vivo and to optimize the ability of crispr / cas to induce recombination of a genomic nucleic acid with an exogenous donor nucleic acid in vivo.

摘要

methods and compositions are provided to assess the crispr / cas-mediated non-homologous (nhej) end-junction activity and / or crispr / cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo or ex vivo. the methods and compositions employ non-human animals comprising a crispr reporter, such as a genomically integrated crispr reporter to detect and measure the targeted excision of a sequence between two crispr / cas nuclease cleavage sites or disrupt a sequence close to a site of crispr / cas nuclease cleavage and / or measuring crispr / cas-induced recombination of the crispr reporter with an exogenous donor nucleic acid to convert the coding sequence to a first reporter protein in the coding sequence to a different second reporter protein . methods and compositions are also provided to produce and use these non-human animals.