Antisense technology involves manipulating or modifying RNA to inhibit the translation of mRNA into proteins, providing a powerful tool for drug discovery and the study of gene function. It employs antisense oligonucleotides, which bind to specific mRNA, disrupting protein synthesis and offering applications in medicine, agriculture, and industry. This approach is particularly beneficial for developing targeted therapeutics for diseases linked to protein production abnormalities, thus expediting drug discovery while reducing costs.

1. ANTISENSE
TECHNOLOGY
ROLE IN DRUG
DISCOVERY
LALITA SHAHGOND
M.PHARM
SEM II
pharmacology

2. Introduction
Conventional definition of antisense:
manipulation and/or modification of DNA or
RNA
so that its component (nucleotides) forms a
complementary copy of normal or “sense”
messenger RNA.

3. What is Antisense technology
• The technique in which translation of mRNA
into proteins is inhibited by introducing single
stranded nucleotide ( oligo de oxy nucleotides)
• The oligonucleotides are complementary to the
mRNA, which physically binds to the mRNA
• This technology prevent the synthesis of
specific proteins.

4. Antisense nucleic acid sequence
+
Specific mRNA
Interrupt normal cellular processing of
gene

5. Antisense technologies are a suite
of techniques that, together form a
very powerful weapon for
studying gene function and for
discovering more specific
treatments of disease.

6. What is Antisense Oligonucleotides
• Oligodeoxynucleotides are 15-20 units
nucleotides, which can hybridize with specific
target mRNA.
• Oligonucleotides can hybridize with
- different types of RNA
- transcripts – mRNAs
- intron-exons
- double stranded RNAs

8. 3 types of anti mRNA strategies
• Using Single stranded antisense
oligonucleotides
• By triggering RNA cleavage through
catalytically active oligonucleotides
(ribozymes)
• RNA interference induced by small
interfering RNAs (siRNA)

10. siRNA
• Known as silencing RNA
• Commonly used RNAi (interference)
• Double stranded RNA, 20-25 base pair,
similar to miRNA and operate with RNA
interference pathway.

12. Application
• Medical application
- in cancer chemotherapy.
- in AIDS therapy.
• Veterinary application
- medicine and pharmaceuticals
- transgenic animals for improved milk
production.

13. - swine fewer, avian flu
• Agricultural application
- genetic application of fruit ripening
- modification of flower color in
decorative flower.
• Industrial application
- new drug discovery

14. Role In Drug Discovery
• In recent years, Antisense oligonucleotides
(AS-OD) technologies have been widely used
as potent and promising tools for drug
discovery and development.
• Diseases are connected to insufficient or
excess production of certain proteins.
• If the production of these proteins are
interrupted then many diseases can be cured.

15. • Antisense technology is a method
which can disrupt protein production.
• it may be used to design new
therapeutics for disease
whose pathology involves specific
protein playing a crucial role

16. • The essential steps in rational drug
design are
- the identification of an
appropriate target responsible for a
certain disease
- development of a drug with a
specific affinity to that target.

17. • One of the most general approaches of
drug targeting is the specific
manipulation of gene expression at the
DNA or RNA stage of protein synthesis.
• No doubt, antisense oligonucleotides
(AS-ODs) are recognized to be very
efficient tools for the inhibition of gene
expression in a sequence-specific way

18. • Drug discovery efforts have
historically focused on the search for
compounds that modulate the protein
products of genes.
• The vast majority of drugs available
today either act at the protein level,
or the drugs themselves are proteins.

19. • It is most advance and genomically
based drug discovery technology.
• Antisense technology provides a
rapid and specific method for
determination of gene function, both
in vitro and in vivo.

20. • The antisense approach could reduce the cost
of drug discovery by expediting the
identification of lead targets for
pharmaceutical intervention.
• Major improvements have been achieved by
the development of modified nucleotides that
provide high target affinity, enhanced
biostability and low toxicity.