Antisense DNA Technology

Abstract

Antisense DNA technology is a method to inhibit or downregulate the production of a target protein by using antisense DNA or RNA molecules. An antisense sequence is a DNA or RNA that is perfectly complementary to the target nucleotide sequence present in the cell. There are two possible mechanisms for an antisense effect. The method that relies on targeting of the mRNA is called the antisense strategy. When the double-stranded DNA or genes situated in the nucleus are targeted, the approach is called the antigene strategy. Whereas the antisense strategy is well established with several examples of in vitro and in vivo applications (1), the antigene approach is still in its infancy and our understanding of the mechanism involved is limited. The antisense strategy utilizes the ability of a 100% complementary DNA or RNA sequence to interlock or hybridize with the target mRNA thus inhibiting the translation of the target protein. This inhibition can be achieved either by blocking the binding sites for the 40S ribosomal subunit and for other translation initiation signals. Alternatively, the formation of a double-stranded DNA/RNA complex can render the RNA susceptible to RNase H digestion (2). The antigene approach is based on the binding of an antisense or sense DNA to the complimentary DNA sequence in the nucleus thus forming a triplex structure. This triplex prevents the transcription of the DNA coding sequence into mRNA (2).