This document provides an overview of antisense oligonucleotide therapy, including its definition as synthetic genetic material that binds to mRNA to prevent protein translation, mechanisms of action such as blocking ribosomes and activating RNase enzymes, applications in oncology and other therapeutic areas, examples of compounds in clinical trials, and its future potential as over 30 compounds are currently in clinical trials.

1. ANTISENSE OLIGONUCLEOTIDE
THERAPY
Presented By-
ROHIT
R.K.S.D college of pharmacy, Kaithal (Hry)
M.Pharma 1st year
(Pharmaceutics)

2. Contents :
 Introduction
 Definition
 Mechanism of action
 Advantages
 Limitations
 Applications
 Examples
 Clinical trials
 Future
 Conclusion

3. Introduction:
 Many pharmacological approach involve
creating compounds that bind and disable
proteins
 For e.g.:
Propranolol which blocks the
ß adrenergic receptors.
Cimitidine which blocks the H2
receptors.

4.  A new way to block protein
function is to prevent the
translation of mRNA into
protein.
 An Antisense
oligonucleotide therapy is
one such approach which
blocks the protein
formation by inhibiting
translation step.

5. Definition:
 Oligonucleotides are chemically
synthesized using phosphoramidites.
 The oligonucleotide chain proceeds in
the direction of 3’ to 5’terminus.
 Antisense oligonucleotides are the
molecules made of synthetic genetic
material, which interact with the natural
genetic material that codes the
information for production of proteins.

6.  Antisense RNA prevent protein translation
of certain mRNA strands by binding to
them.
 Antisense DNA can be used to target a
specific complementary RNA.

7. Mechanism of action of antisense
therapy:

8. Translational arrest by blocking
ribosome.

9. Activation of RNase enzyme:

10. Triplex antisense technology
(ANTIGENE)

11. Inhibition of angiotensinogen by
antisense oligonucleotide therapy

12. Advantages:
 Oligonucleotides are manufactured
quickly I.e. within a week.
 Sensitivity of therapy can be easily
measured.
 Potential to produce longer lasting
responses.
 Potential for enhanced binding affinity
to target.

13. Limitations:
 Antisense agents have to be protected
against nucleolytic attack.
 Large doses are required for
therapeutic response.
 The difficulty in directing to a particular
cells.
 The half-life in plasma is short.

14. Antisense
oligonucleotide
therapy
oncology
CVS & CNS
therapeutics
As
Antiviral and
antibacterial
agent.
Inflammation
therapeutics
A
P
P
L
I
C
A
T
I
O
N
S

15.  Other disease
states like:
 Diabetes
Amyotrophic lateral
sclerosis(ALS)
Duchene muscular
dystrophy
 Asthma
Hair loss.

16. Role in Genomics:
ic
.
d
e
Antisense therapy in genom
technology provide:
 Ease of protein synthesis
Target of a single intende
gene.
Quick reproducible
laboratory results.
Genes responsible for th
cause of disease can be
predicted.

17.  Technetium-99m labeled antisense
probes are radiolabelled agents. These
are injected intravenously and those are
imaged in early stages.

18. Examples:
 Fomivirsen for the treatment of
cytomegalovirus retinits.
 Mipomersen for high cholesterol.
 Affinitak and Genasense against
cancer.
 AV 1-6002 & AV 1-6003 for the
treatment of Hemorrhagic fever.
 AP 1-2009 for the treatment of high
grade gliomas.

19. Product Sequenc
e
Target Disease
Vitravene GCGTTTGCTCT
TCTTCTTGCG
IE 2 Cytomegaloviru
s retinitis.
Affinitak GTTCTCGCTGG
TGAGTTTCA
PKC-α Cancer
Genasens
e (genta)
TCTCCCAGC
GTGCGCCAT
BCl 2 Cancer

20. Clinical trials:
 In 1996 only a handful of
antisense molecules was
in clinical trials.
 Currently there are
nearly 50 antisense
compounds are under
clinical trials for various
diseases, out of them 10
are under phase III & 30
are under phase II
clinical trials.

21. Future of antisense based
technology:
 Currently over 30 pharmaceutical
& biotechnology companies have
declared an interest in developing
the antisense based therapeutics.

22. Conclusion:
 Antisense oligonucleotide therapy
blocks the translation process where
there is no formation protein
responsible for a particular disease.