ANTISENSE THERAPHY

1. ANTISENSE OLIGONUCLEOTIDES
AYANA R KUMAR
M Pharm, Pharmacology
DEPARTMENT OF PHARMACOLOGY 1

2. ANTISENSE OLIGONUCLEOTIDE
 Antisense RNA (as RNA)
 Antisense transcript
 Natural Antisense Transcript (NAT)
 Single stranded RNA
DEPARTMENT OF PHARMACOLOGY 2

3. ANTISENSE TECHNOLOGY
 Antisense therapy
 Regulate gene expression
 Gene knock down
Fomivirsen - Cytomegalovirus retinitis
Mipomersen - Hypercholesterolemia
Eteplirsen – Muscular dystrophy
Nusinersen - Spinal muscular atrophy.
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4. DEPARTMENT OF PHARMACOLOGY 4

5. CLASSIFICATION
• Cis – acting oligonucleotide
• Trans – acting oligonucleotide
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6. MECHANISM OF ACTION
(a)The RNAse H-dependent oligonucleotides - Degradation of
mRNA.
(b) The steric blocker oligonucleotides - Physically prevent or inhibit
the progression of splicing or the translational.
DEPARTMENT OF PHARMACOLOGY 6

7. DEPARTMENT OF PHARMACOLOGY 7

8. DELIVERY OF OLIGONUCLEOTIDES TO CELL
 Uptake occurs through active transport
 Temperature
 The structure
 Concentration of the oligonucleotide
• Adsorptive endocytosis
• Fluid phase pinocytosis
DEPARTMENT OF PHARMACOLOGY 8

9. FUNCTIONS
 Epigenetic regulation
 DNA methylation
 Histone modification
 Co-transcriptional regulation
 Post-transcriptional regulation
DEPARTMENT OF PHARMACOLOGY 9

10. ANTISENSE OLIGONUCLEOTIDE
TECHNOLOGIES IN DRUG DISCOVERY
 New genomic knowledge.
 Simple and Efficient.
 Specific manipulation of gene expression at the
DNA or RNA stage of protein synthesis.
 Gene-function analysis and for the development
of therapeutics.
 Target-gene function.
 Identification of novel drug targets.
 Function of any newly discovered genes.
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11.  Discover novel pathways
 Design new, gene-specific drug targets.
 Reduce the cost of drug discovery
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12. DEPARTMENT OF PHARMACOLOGY 12

13. REFERENCES
1. Expert opin. Drug Discov. (2006), 1 (4): 285 – 288.
2. Antisense Oligonucleotides: Basic Concepts and Mechanisms
.Dol Nathalie Dias Published March 2002.
3. Agrawal s, kandimalla .Antisense therapeutics: is it as simple
as complementary base recognition. Mol. Med. Today (2000)
6:72-81.
4. hopkins al groom cr. The druggable genome. Nat. Rev. Drug
Discov. (2002) 1:727-730.
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14. THANK YOU
DEPARTMENT OF PHARMACOLOGY 14