Methods and compositions for effecting homologous recombination

摘要

This invention concerns a method for effecting homologous recombination between a native nucleic acid segment in a cell and a donor nucleic acid segment introduced into the cell, which comprises : a) introducing into a cell a nucleic acid delivery system comprising: (i) an oligonucleotide third strand which comprises a base sequence capable of forming a triple helix at a binding region on one or both strands of a native nucleic acid segment, (ii) a donor nucleic acid, comprising a nucleic acid sequence sufficiently homologous to the native nucleic acid segment such that the donor sequence is capable of undergoing homologous recombination with the native sequence at the target region, (iii) an adapter segment comprising an oligonucleotide sequence able to bind at least a portion of said donor nucleic acid through Watson-Crick base pairing, the adapter segment being linked to said oligonucleotide third strand, b) allowing the oligonucleotide to bind to the native nucleic acid segment to form a triple helix nucleic acid, thereby inducing homologous recombination at the native nucleic acid segment target region ; and c) allowing homologous recombination to occur between the native and donor nucleic acid segments. The method may namely be implemented for effecting gene alteration or mutation repair at a specific sequence site on a native DNA. <IMAGE>