Positive-negative selector (PNS) vectors are provided for modifying a
target DNA sequence contained in the genome of a target cell capable of
homologous recombination. The vector comprises a first DNA sequence which
contains at least one sequence portion which is substantially homologous
to a portion of a first region of a target DNA sequence. The vector also
includes a second DNA sequence containing at least one sequence portion
which is substantially homologous to another portion of a second region
of a target DNA sequence. A third DNA sequence is positioned between the
first and second DNA sequences and encodes a positive selection marker
which when expressed is functional in the target cell in which the vector
is used. A fourth DNA sequence encoding a negative selection marker, also
functional in the target cell, is positioned 5' to the first or 3' to the
second DNA sequence and is substantially incapable of homologous
recombination with the target DNA sequence. The invention also includes
transformed cells containing at least one predetermined modification of a
target DNA sequence contained in the genome of the cell. In addition, the
invention includes organisms such as non-human transgenic animals and
plants which contain cells having predetermined modifications of a target
DNA sequence in the genome of the organism.
