Gene Silencing

Introduction

Gene silencing.
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

Note: antisense and RNAi are refered as gene knockdown technologies: the transcription of the gene is unaffected; however, gene expression, i.e. protein synthesis, is lost because mRNA molecules become unstable or unaccessible. Furthermore, RNAi is based on naturally occurring phenomenon known as Post-Transcriptional Gene Silencing (PTGS).

Probe

Resources