Synthesis of designed antisense RNAs

Synthesis of designed antisense RNAs is being widely used as an approach to gene knockdown, when an investigator wishes to block expression of a specific gene without the extensive efforts involved in creating knockout organisms by targeted gene interruption.

A synthetic oligonucleotide can be introduced into cells, usually following treatment to transiently increase membrane permeability, with a sequence targeted to the gene whose expression is to be inhibited.

Often the knockdown reagent is not an RNA molecule but an RNA analog, one that has been modified so as to avoid enzymatic degradation within the cell.

A popular family of antisense reagents is the morpholinos, oligomers or polymers that use the same bases as found in natural RNA, but which have morpholine instead of ribose and a phosphorodiamidate bond to link adjacent “nucleotide” units.