The present invention provides compositions and methods for utilizing a large capacity cloning vector (e.g., BAC) to carry a large exogenous genomic DNA (about 10-300 kb) flanked by a proximal and distal regions (10 kb) to efficiently insert into the genome of a cell in a CRISPR/Cas9-stimulated homologous recombination. Methods and compositions for microinjecting a large human gene into a mouse zygote to prepare a genetically modified mouse are also provided.
