FIELD: biotechnology.
SUBSTANCE: present invention relates to genetic engineering. Presented is an in vitro method of modifying a genome in a genome locus of interest in a non-human pluripotent cell of a mammal, comprising adding into the cell components of the CRISPR/Cas9 system in combination with a large guide vector (LTVEC), which is at least 10 kb.
EFFECT: present invention enables genetic modification of a cell by deleting from about 30 kb up to 200 kb and/or insert from about 30 kb to about 200 kb.
70 cl, 55 dwg, 48 tbl, 6 ex
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