Antisense Technology

Delihas, N (2001) Antisense Nucleic Acids in Biotechnology. Encycloptedia of Life Sciences,

Nature publishing

Nucleic Acid Drugs

Antisense oligonucleotidesto block translation of a particular protein

Small interfering RNAsmicro RNAsRNA interference

Features

Short synthetic oligonucleotides – DNA,RNA Target

Cellular RNASpecific block in transcriptionRNA splicing/transporttranslation

Viral RNA Length to guarantee theoretical uniqueness

Human genome 3.0 x 109 bp 16 mer Celluar RNA 1.5 x 107 bp 12 mer Min. 12 mer Typically 18 merMax. 24 mer

Modification to resist Dnase degradation Inclusion of phosphorothioate groups

Stability of RNA oligonucleotides

In 95% serum at 37℃

Principal target sites

Transcription DNA triple helix formation Hybridization to DNA

loops Hybridization to nascent

RNA RNA processing

RNA splicing RNA transport

Translation Inhibition of initiation

factor binding Inhibition of ribosome

assembly Inhibition of movement

Targeting

In theory : target AUG start codon In practice : trial and error

mRNA degradation

RNase H – ribonuclease that recognizes and cleaves mRNA in an RNA/DNA duplex