Antisense & RNAi

Antisense therapy involves single stranded nucleic acids that are usually highly modified. They act by one of three general mechanisms: 1) cleavage of a DNA/RNA hybrid portion by RNase H for gene silencing, 2) steric blocking of translational initiation for gene silencing, or 3) steric blocking of splice site donors or acceptors to mediate splice switching. RNAi relies on small interfering RNAs (siRNAs) that are generally 21-23 nucleotide duplex RNAs with 2 base 3’ overhangs. Upon transfection into cells, the guide strand of the siRNA duplex is incorporated into the RNA induced silencing complex (RISC). RISC then cleaves mRNAs with homology to the guide strand, silencing them.