This document discusses antisense oligonucleotides, which are single-stranded RNA molecules that regulate gene expression by binding to mRNA. Antisense oligonucleotides have been developed as therapeutics to treat conditions like cytomegalovirus retinitis, hypercholesterolemia, and muscular dystrophy. They work either by recruiting RNase H to degrade mRNA or by physically blocking translation. Delivery of antisense oligonucleotides into cells occurs through endocytosis or fluid-phase pinocytosis. Antisense technologies can be used in drug discovery to specifically manipulate gene expression and identify novel drug targets.

1. ANTISENSE OLIGONUCLEOTIDES
AYANA R KUMAR
M Pharm, Pharmacology
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2. ANTISENSE OLIGONUCLEOTIDE
 Antisense RNA (as RNA)
 Antisense transcript
 Natural Antisense Transcript (NAT)
 Single stranded RNA
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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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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.
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8. DELIVERY OF OLIGONUCLEOTIDES TO CELL
 Uptake occurs through active transport
 Temperature
 The structure
 Concentration of the oligonucleotide
• Adsorptive endocytosis
• Fluid phase pinocytosis
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9. FUNCTIONS
 Epigenetic regulation
 DNA methylation
 Histone modification
 Co-transcriptional regulation
 Post-transcriptional regulation
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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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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
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