Inventors:
Gloria C. Li - New York NY, US
Paul W. J. J. Burgman - New York NY, US
Assignee:
Sloan-Kettering Institute for Cancer Research - New York NY
International Classification:
A01N 43/04, A01N 61/00, C12Q 1/68, C12N 15/63, C07H 21/04
US Classification:
514 44, 435 6, 435 911, 4353201, 435455, 514 1, 514 2, 536 231, 536 245
Abstract:
This invention provides a method for increasing the susceptibility of a cell to DNA-damaging agents, comprising introducing into the cell an antisense oligonucleotide that specifically hybridizes to a nucleic acid encoding a DNA dependent protein kinase subunit so as to prevent expression of the DNA dependent protein kinase subunit; wherein the antisense oligonucleotide is in an amount sufficient to increase the sensitivity of the cell to heat, chemical, or radiation-induced DNA damage; and wherein the DNA dependent protein kinase subunit is a DNA dependent protein kinase catalytic subunit, a Ku70, or a Ku80. This invention also provides a method of treating a tumor in a subject, comprising administering to the subject an antisense oligonucleotide that specifically hybridizes to a nucleic acid encoding a DNA dependent protein kinase subunit so as to prevent expression of the DNA dependent protein kinase subunit; wherein the antisense oligonucleotide is in an amount sufficient to increase the sensitivity of the tumor to heat, chemical or radiation-induced DNA damage; and wherein the DNA dependent protein kinase subunit is a DNA dependent protein kinase catalytic subunit, a Ku70, or a Ku80. This invention provides an antisense oligonucleotide that specifically hybridizes to a nucleic acid encoding a DNA dependent protein kinase subunit, wherein the DNA dependent protein kinase subunit is a DNA, dependent protein kinase catalytic subunit, Ku70, or Ku80, so as to prevent expression of the DNA dependent protein kinase subunit.