Pseudocomplementary Oligonucleotides for Targeted Gene Therapy

Abstract

Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.

Dependencies are inferred from the claim text.