Targeted chromosomal genomic alterations with modified single stranded oligonucleotides

摘要

Methods of targeted chromosomal sequence alteration, the methods 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 more mismatches positioned (i) within said oligonucleotide's unmodified DNA domain and (ii) at least 8 nucleotides from each of said oligonucleotide's 5' and 3' termini; and has at least one terminal chemical modification, whereby said introduced oligonucleotide directs sequence alteration by the cellular recombination or repair enzyme machinery at said chromosomal target sequence.