Abstract: An oligonucleotide based therapeutic strategy, called anti-gene locks, is described which specifically kills cells based on their genotype. The strategy employs oligonucleotides with arms and a backbone that are complementary to both strands of the gene target. Anti-gene locks bind in vitro in a sequence dependent fashion and inhibit DNA synthesis. In bacterial cells containing an episome target, they cause elimination of the extra-chromosomal DNA structure. When the target is present in the bacterial or human genome, they selectively kill the majority of these cells.