Biomedical Engineering Reference
In-Depth Information
Table 7.4
AS ODNs Versus RNAi
S. No.
AS ODNs
RNAi
1.
Single-stranded 12-22 mer DNA
oligonucleotides complementary to
the target mRNA sequence silence the
expression of the target gene.
19- to 23-nucleotide long double-stranded
siRNAs target gene silencing.
2.
AS ODNs exert a gene-silencing
effect mostly by steric inhibition of
translation by the ribosomal complex
or by activating RNase H to cleave the
target RNA molecule.
The mechanism involves sequential
cleavage of long dsRNA by the enzyme
Dicer RNase III into siRNAs, which are
then incorporated into a complex termed
RISC to target the degradation of mRNA
transcript.
3.
These can either act on DNA to
interfere in mRNA transcription or
may interact with mRNA.
siRNA specifically interferes at the
posttranscriptional phase to perform the
gene-silencing action.
4.
Target sequence identification and
oligonucleotide design is difficult due
to unknown secondary RNA structure.
Target sequence identification and oligo
design is easier than for AS ODNs.
5.
They require higher concentration to
exert their action.
Gene silencing occurs at much lower
concentration.
6.
Gene silencing induced by
oligonucleotides is short lived.
Stable incorporation of siRNA into RISC
leads to prolonged gene silencing.
7.
AS ODNs result in a less potent gene-
silencing effect than siRNA.
siRNA results in significantly greater
gene-silencing effect at such a lower
concentration than AS ODNs that it
becomes difficult even to detect them.
8.
Being highly target specific, AS
ODNs induce many fewer “off-target”
effects.
Though highly target specific, siRNAs
may induce significant “off-target” effects,
depending on the length and siRNA
design.
9.
AS ODNs can cross the cell
membrane comparatively faster as
compared to siRNAs.
Because of their large molecular mass
(twice that of single-stranded AS ODNs)
and high negative charge, siRNAs do not
readily cross the cell membrane.
10.
Mostly AS ODNs need to enter the
nucleus for effective gene silencing.
siRNA does not require nuclear access
and exhibits its action by target mRNA
degradation in the cytoplasm.
doi:10.1093/ndt/gfn095 and doi:10.1016/j.drudis.2008.03.014
siRNAs can be produced chemically as well as enzymatically and introduced directly into
the cell with or without minimal interferon response as compared to the long dsRNA. Since
1998, many studies have been executed to evaluate the therapeutic potential of siRNA,
and pharmaceutical industries have invested billions on this technology through licensing
delivery platforms and strategic alliances in the development of RNAi-based therapeutic
products. Initially, the studies were limited to local administration of siRNA for the
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