Antisense oligonucleotide therapy is a pharmacological approach that uses synthetic genetic material to inhibit protein translation by binding to mRNA. It works by blocking ribosomes, activating RNase enzymes, or forming triplex structures. Advantages include rapid manufacturing and potential for enhanced targeting. Limitations include short half-lives and difficulty directing to specific cells. Over 50 antisense compounds are in clinical trials for various diseases. The future of antisense-based therapies looks promising as more companies develop applications.

1. welcome

2. ANTISENSE OLIGONUCLEOTIDE THERAPY UNDER GUIDENCE OF:Mrs. GeetaAssociate ProfessorDept of BiotechnologyBY:G.RaginiM.PharmPharmacology.10T21S0114

3. Contents :IntroductionDefinitionMechanism of actionAdvantagesLimitations ApplicationsExamplesClinical trialsFuture Conclusion

4. Introduction:Many pharmacological approach involve creating compounds that bind and disable proteinsFor e.g.: Propranolol which blocks the ß adrenergic receptors. Cimitidine which blocks the H2 receptors.

5. A new way to block protein function is to prevent the translation of mRNA into protein.An Antisense oligonucleotide therapy is one such approach which blocks the protein formation by inhibiting translation step.

6. Definition: Oligonucleotides are chemically synthesized using phosphoramidites.The oligonucleotide chain proceeds in the direction of 3’ to 5’ terminus.Antisense oligonucleotides are the molecules made of synthetic genetic material, which interact with the natural genetic material that codes the information for production of proteins.

7. Antisense RNA prevent protein translation of certain mRNA strands by binding to them.Antisense DNA can be used to target a specific complementary RNA.

8. Mechanism of action of antisense therapy:

9. Translational arrest by blocking ribosome.

10. Activation of RNase enzyme:

11. Triplex antisense technology (ANTIGENE)

12. Inhibition of angiotensinogen by antisense oligonucleotide therapy

13. Advantages:Oligonucleotides are manufactured quickly I.e. within a week.Sensitivity of therapy can be easily measured.Potential to produce longer lasting responses.Potential for enhanced binding affinity to target.

14. Limitations:Antisense agents have to be protected against nucleolytic attack. Large doses are required for therapeutic response.The difficulty in directing to a particular cells.The half-life in plasma is short.

15. APPLICATIONS

16. Other disease states like: Diabetes

17. Amyotrophic lateral sclerosis(ALS)

18. Duchene muscular dystrophy

19. Asthma

20. Hair loss.Role in Genomics: Antisense therapy in genomic technology provide: Ease of protein synthesis.

21. Target of a single intended gene.

22. Quick reproducible laboratory results.

23. Genes responsible for the cause of disease can be predicted. Technetium-99m labeled antisense probes are radiolabelled agents. These are injected intravenously and those are imaged in early stages.

24. Examples:Fomivirsen for the treatment of cytomegalovirus retinits.Mipomersen for high cholesterol.Affinitak and Genasense against cancer.AV 1-6002 & AV 1-6003 for the treatment of Hemorrhagic fever.AP 1-2009 for the treatment of high grade gliomas.

26. Clinical trials:In 1996 only a handful of antisense molecules was in clinical trials.Currently there are nearly 50 antisense compounds are under clinical trials for various diseases, out of them 10 are under phase III & 30 are under phase II clinical trials.