Antisense oligonucleotide therapy

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Antisense oligonucleotide therapy

  1. 1. welcome<br />
  2. 2. ANTISENSE OLIGONUCLEOTIDE THERAPY <br />UNDER GUIDENCE OF:<br />Mrs. Geeta<br />Associate Professor<br />Dept of Biotechnology<br />BY:<br />G.Ragini<br />M.Pharm<br />Pharmacology.<br />10T21S0114<br />
  3. 3. Contents :<br />Introduction<br />Definition<br />Mechanism of action<br />Advantages<br />Limitations <br />Applications<br />Examples<br />Clinical trials<br />Future <br />Conclusion<br />
  4. 4. Introduction:<br />Many pharmacological approach involve creating compounds that bind and disable proteins<br />For e.g.:<br /> Propranolol which blocks the <br /> ß adrenergic receptors.<br /> Cimitidine which blocks the H2 receptors.<br />
  5. 5. A new way to block protein function is to prevent the translation of mRNA into protein.<br />An Antisense oligonucleotide therapy is one such approach which blocks the protein formation by inhibiting translation step.<br />
  6. 6. Definition: <br />Oligonucleotides are chemically synthesized using phosphoramidites.<br />The oligonucleotide chain proceeds in the direction of 3’ to 5’ terminus.<br />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.<br />
  7. 7. Antisense RNA prevent protein translation of certain mRNA strands by binding to them.<br />Antisense DNA can be used to target a specific complementary RNA.<br />
  8. 8. Mechanism of action of antisense therapy:<br />
  9. 9. Translational arrest by blocking ribosome.<br />
  10. 10. Activation of RNase enzyme:<br />
  11. 11. Triplex antisense technology (ANTIGENE)<br />
  12. 12. Inhibition of angiotensinogen by antisense oligonucleotide therapy<br />
  13. 13. Advantages:<br />Oligonucleotides are manufactured quickly I.e. within a week.<br />Sensitivity of therapy can be easily measured.<br />Potential to produce longer lasting responses.<br />Potential for enhanced binding affinity to target.<br />
  14. 14. Limitations:<br />Antisense agents have to be protected against nucleolytic attack.<br /> Large doses are required for therapeutic response.<br />The difficulty in directing to a particular cells.<br />The half-life in plasma is short.<br />
  15. 15. A<br />P<br />P<br />L<br />I<br />C<br />A<br />T<br />I<br />O<br />N<br />S<br />
  16. 16. Other disease states like:<br /><ul><li> Diabetes
  17. 17. Amyotrophic lateral sclerosis(ALS)
  18. 18. Duchene muscular dystrophy
  19. 19. Asthma
  20. 20. Hair loss.</li></li></ul><li>Role in Genomics:<br /> Antisense therapy in genomic technology provide: <br /><ul><li> Ease of protein synthesis.
  21. 21. Target of a single intended gene.
  22. 22. Quick reproducible laboratory results.
  23. 23. Genes responsible for the cause of disease can be predicted.</li></li></ul><li> Technetium-99m labeled antisense probes are radiolabelled agents. These are injected intravenously and those are imaged in early stages.<br />
  24. 24. Examples:<br />Fomivirsen for the treatment of cytomegalovirus retinits.<br />Mipomersen for high cholesterol.<br />Affinitak and Genasense against cancer.<br />AV 1-6002 & AV 1-6003 for the treatment of Hemorrhagic fever.<br />AP 1-2009 for the treatment of high grade gliomas.<br />
  25. 25.
  26. 26. Clinical trials:<br />In 1996 only a handful of antisense molecules was in clinical trials.<br />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.<br />
  27. 27. Future of antisense based technology:<br />Currently over 30 pharmaceutical & biotechnology companies have declared an interest in developing the antisense based therapeutics.<br />
  28. 28. Conclusion:<br />Antisense oligonucleotide therapy blocks the translation process where there is no formation protein responsible for a particular disease.<br />
  29. 29. THE PROMISE OF ANTISENSE BASED BIOTECHNOLOGY IS THEREFORE STRONGER THAN EVER…….<br />
  30. 30. QUERIES….????<br />
  31. 31. Thank you<br />

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