Patent ID: 6936467

Claim:
A method of targeted alteration of a chromosomal sequence present within a cell in vitro, the method comprising: introducing a sequence-altering oligonucleotide into a cell in vitro, wherein said sequence-altering oligonucleotide: is a single-stranded nonhairpin oligonucleotide 17-121 nucleotides in length; has an unmodified DNA domain of at least 8 contiguous deoxyribonucleotides; is fully complementary in sequence to a first strand of the cell's chromosomal DNA at a chromosomal target sequence, except for one or two mismatches positioned (i) within said oligonucleotide's unmodified DNA domain and (ii) at least 8 nucleotides from said oligonucleotide's 5′ and 3′ termini; and has chemical modifications consisting essentially of at least one terminal locked nucleic acid (LNA), or at least one terminal 2′-O-Me base analog, or at least three terminal phosphorothioate linkages, or combinations thereof, and wherein said cell is not a human embryonic stem cell, whereby said introduced oligonucleotide directs sequence alteration at said chromosomal target sequence by the cellular repair enzyme machinery.