Gene Silencing:

BY

SHAKIRA SULEHRI

2013

Gene Silencing:

The term gene silencing is generally used to describe the "switching off" of a gene by a mechanism other than genetic modification. That is, a gene which would be expressed (turned on) under normal circumstances is switched off by machinery in the cell.

Interruption or suppression of the expression of a gene at transcriptional or translational levels. Scientists have been working on strategies to selectively turn off specific genes in diseased tissues for the past thirty years:

1980's - antisense oligodeoxynucleotides (ODNs)

1990's - ribozymes

2000's - RNA interference (RNAi)

Comparison of different gene silencing strategies.

Agent Mechanism Result

Most drugs Bind to target protein Protein inhibition

RNase H-

independent

ODNs

Hybridize to target mRNA Inhibition of

translation of the

target protein

RNase H-

dependent

ODNs

Hybridize to target mRNA Degradation of the

mRNA by RNase H

Ribozymes and

DNA enzymes

Catalyze cleavage of target mRNA Degradation of the

mRNA

siRNA Hybridize to target mRNA by its antisense

strand and guide it into endoribonuclease

enzyme complex (RISC)

Degradation of the

mRNA

Comparison of gene silencing strategies