Antisense technology

siRNA, antisense oligonucleotides, drug discovery, antisense technology, antisense drug therapy, types of anti mRNA strategy

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 O ligonucleotides 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

7. 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)

8. 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.

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

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

11. 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.

12. 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

13. 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.

14. 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

15. 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.

16. 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.

17. 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.