Antisense Oligonucleotides and RNA Interference - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 348

Table 7.5 siRNA Versus miRNA

S. No. siRNA miRNA

1. siRNA is synthesized from double-

stranded segments of matched mRNA
via RNA-dependent RNA polymerase.

miRNA is synthesized from an unmatched
segment of RNA precursor featuring a
hairpin foldback structure.

2. The precursor of endogenous siRNA

is a long dsRNA.

The precursor of a miRNA is hairpin-
shaped RNA.

3. Each dsRNA precursor gives rise to

numerous different siRNAs.

Each hairpin is processed to ultimately
accumulate a single miRNA molecule
from one arm of each hairpin precursor
molecule.

4. siRNAs may be endogenous or

exogenously derived from viruses.

miRNAs are entirely endogenous.

5. siRNAs generally exhibit less sequence

conservation.

Sequences of the mature miRNAs and
their hairpin precursors are usually
evolutionarily conserved.

6. siRNAs are synthesized from RNA-

dependent RNA polymerase and
processed from Dicer enzymes.

miRNAs are synthesized from RNA
polymerase-II and processed from Drosha
and Dicer enzymes.

7. The main function of siRNAs is

cleavage of mRNA.

Mainly, miRNAs inhibit protein synthesis
by blocking mRNA translation; however,
cleavage of mRNA may also be there.

8. siRNAs are affecter molecules of

RNAi pathway.

miRNAs are encoded in the genome to
regulate natural gene expression.

9. siRNAs are involved in natural cellular

defense mechanism.

miRNAs regulate critical biological
processes from growth and development,
to oncogenesis and host-pathogen
interaction.

10. siRNAs often perfectly correspond to

the sequences of known or predicted
mRNAs, transposons, or regions of
heterochromatic DNA.

miRNAs rarely correspond perfectly to
the sequences of mRNAs targets and are
derived from loci distinct from those of
their mRNA targets.

7.7 Pharmacokinetics and Pharmacodynamics

The development of various sensitive analytical methods to selectively quantify oligo-
nucleotides in biological systems has made it possible to study the metabolism of these
compounds easily [131-133] . However, because the pharmacokinetics of oligonucle-
otides has been reported to be sequence independent, data from one sequence can be
used to understand pharmacokinetics of the entire class [134,135] . Under pharmaco-
kinetics, we discuss the kinetics of antisense drugs, clearance of drugs from the site of
action, and its ultimate pharmacological activity. Because phosphorothioate oligonucle-
otides are the most widely studied, we discuss the AS ODN kinetics with respect to the
pharmacokinetics of phosphorothioate oligonucleotides [135,136] .