Disclosed herein are siHybrids used for gene silencing. An siHybrid is a short double-stranded molecule comprised of one strand of DNA and one strand of RNA, annealed together, with a 2-base overhang at each 3′ end. In addition to DNA and RNA, it may contain PNA or other nucleic acid analogs. siHybrids can silence a gene with greater magnitude and duration than siRNA. sihybrids are ideal candidates for pharmaceutical and therapeutic agents for treating diseases caused by an over-expressed gene or a cancerous gene. siHybrids can be used as antivirus agents, fungicides, herbicides or pesticides. An appropriate siHybrid can be designed to silence any gene in any eukaryotic cell or organism.
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