Antisense therapy is an approach to fighting diseases using short DNA-like molecules called antisense oligonucleotides.

1. ANTISENSE
OLIGONUCLEOTIDES
PRESENTED BY
GAIKWAD ASHWINI ABHIMANYU
M. PHARM. 1ST YEAR ( SEM -II)
PHARMACOLOGY

2. CONTENT
• INTRODUCTION
• DEFINITION
• MECHANISM
• CHARACTERISTICS
• ADVANTAGES
• DISADVANTAGES
• FUNCTIONS
• APPLICATIONS

3. ●Many pharmacological approaches involve
creating compound that binds and disable
proteins.
For e.g. :
Propranolol blocks the beta adrenergic receptors.
Cimetidine blocks the H2 receptors.
INTRODUCTION

4. ●A new way to block protein function is
to prevent the translation of mRNA into
protein .
●An antisense oligonucleotides therapy
is one such approach which block the
protein formation by inhibiting
translation step.

5. Oligonucleotides are chemically synthesized using phosphoramidites.
Antisense oligonucleotides are molecules made of synthetic genetic
material which interact with the natural genetic material that codes the
information.
Antisense RNA prevent protein translation of certain mRNA strands by
binding to them .
Antisense DNA can be used to a specific complementary RNA.
DEFINITION

6. ●The concept of antisense oligonucleotides gene silencing was first
introduced in 1978 when Stephenson and Zameenik used an antisense
oligonucleotides to stop viral replication in cell culture.
●An antisense oligonucleotides is a single strand of nuclei acid and nuclei
acid analogs , most often an oligodeoxyribonucleotide, usually 15- 20
molecules in length with sequence complementary to a specific target mRNA .
●An antisense oligonucleotides and target mRNA bind together via Watson
crick has base pairing and his hybridization leads to reduce the level of
translation of the specific transcript.

7. Once ASO bind to target RNA sequence, ASO regulate the
function of target RNA through broad set of mechanism.
1)Bind to RNA and hinder it’s function without facilitating
RNA degradation such as translation inhibit or modulation
of RNA processing.
2)Promote degradation of RNA via endogenous enzymes,
such as RNAseH or argonaute – 2 ( RNA interference
RNAi ).

8. MECHANISM

9. Mechanism
●In these technique , Short segment of single stranded RNA are
introduced.
●These oligonucleotides are complementary to mRNA which
physically bind to mRNA.
●So , they block the expression of particular gene .
●In case of viruses, antisense oligonucleotides inhibits viral
Replication by blocking expression of integrated proviral gene .
●Usually consist of 15-20 nucleotides.

11. Inhibition of angiotensinogen by antisense oligonucleotides therapy

12. Characteristics of antisense oligonucleotides
●Unique DNA sequence
●Efficient cellular uptake
●Minimal nonspecific binding
●Target specific hybridization
●Non- toxic antisense construct

13. ADVANTAGES
1)Manufactured quickly
2)Sensitivity easily measured
3)Longer lasting response
4)Enhanced binding affinity to target

14. 1)Antisense agents are protected against nucleolyatic attack
2)Large dose required
3)Target direction difficult
4)Half – life in plasma , short
DISADVANTAGES

15. FUNCTIONS
●Epigenetic regulation
●DNA methylation
● Histone modification
●Co-transcriptional regulation
●Post-transcriptional regulation

16. APPLICATIONS
●Antisense oligonucleotide therapy
1. Oncology
2. CNS & CVS therapies
3. As antiviral and antibacterial agent
4. Inflammation therapeutics
●Other disease state like
1. Diabetes
2. Asthma
3. Hair loss
4. Duchene muscular dystrophy
5.Amyotrophic lateral sclerosis