Gene therapy - current status and future perspective

Discussing what gene therapy is, its types and methods used.

1. INTRODUCTION TO GENE THERAPY: CURRENT STATUS & FUTURE PERSPECTIVE ALEENA HAQQI KHUSHBAKHT KHAN KAFILA KOUSAR HANIA SHAH FAIZA NASEER SUMAIYA LIAQUAT COURSE : PRINCIPLES OF MOLECULAR BIOLOGY

2. 2 CONTENTS Introduction To Gene Therapy Gene Therapy Types Steps Involved In Gene Therapy Applications Current Status Limitations Future Perspective

3. Introduction to gene therapy By Sumaiya Liaquat

4. 4 Introduction To Gene Therapy Correction of Abnormal Gene Therapeutic delivery of nucleic acid into a patient's cells

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7. 7 TYPES BASED ON TECHNIQUES USED

8. 8

9. 9 TYPES BASED ON CELL TYPE

10. 10 TYPES OF SOMATIC CELL THERAPY

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12. 3

13. Steps involved in gene therapy By ALEENA HAQQI

14. 14 STEPS INVOLVED

15. 16 Specific Efficient Delivery Non- Immunogenic Non-Inflammatory Safe for patient & Enviroment Long term Expression SELECTION OF VECTOR

16. 17

17. 15 Higher Transgene Capacity Important Sequence required to Insert DNA Promoter Sequence Inverted Terminal Repeat Control Elements Antibiotic Resistant Gene Genes Essential for Viral Enzymes SELECTION OF PLASMID

18. 19 GENE DELIVERY SYSTEM

19. Applications of gene therapy By Kafila Kousar

20. 22 Replace Missing or defective gene Deliver Gene That speed the destructio of cancer cells or revert them back to normal Deliver Viral or Bacterial gene as a form of vaccination Deliver Gene that stimulate the healing of a wound Deliver Gene to treat genetic disorders Provide genes that promote or impede the growth of new tissue APPLICATIONS

21. 23 APPLICATIONS

22. 24 APPLICATIONS

23. 25 APPLICATIONS

24. Current status of gene therapy By Khushbakht Khan

25. 27 HISTORY OF GENE THERAPY

26. 3 1990 – 2015 : 2335 2018: 2731 Monogenic diseases Cancer 64.41% Pharmaceutical Research and Manufacturers of America ( PhRMA ) 771 new oncology drugs and vaccines currently in clinical trials or submitted to FDA for review in US companies . GENE THERAPY-CURRENT STATUS

27. 29 CLINICAL TRIALS DISTRIBUTION OF GENE THERAPY CLINICAL TRIALS BY COUNTRY

28. 30 CLINICAL TRIALS PHASE OF DEVELOPMENT OF GENE THERAPY CLINICAL TRIALS Among which, 30% are cancer therapies.

29. 31 VECTORS FOR GENE THERAPY Only causes a mild immune response. Infects both dividing and non-dividing cells. Remains in an extra-chromosomal state.

30. 32 Help medicine developers prepare marketing authorization applications for human medicines. Safety and control measures associated with gene therapy. Reviews gene therapy protocols Financial Support General Cost $375,000 and $875,000 GENE THERAPY REGULATIONS

31. 3 RECENT GENE THERAPY DRUGS Disease Drug Company β- thalassemia Zynteglo Bluebird Bio Spinal muscular atrophy Zolgensma Novartis RPE65 deficiency Luxturna Spark Head and neck squamous cell carcinoma Gendicine Shenzhen SiBionoGeneTech ($2.1 million / patient) ($2.125 million / patient) ($425,000 / eye) ($387 / injection)

32. Limitations gene therapy By Faiza Naseer

33. 35 LIMITATIONS OF GENE THERAPY

34. 36 LIMITATIONS

35. 37 LIMITATIONS

36. 38 LIMITATIONS Religious Values No Comments

37. Future perspective of gene therapy By Hania Shah

38. 40 TREATMENT Gene therapy has the potential to change; The conventional symptomatic approach to disease treatment Provide options for diseases that cannot be treated in any other way.  So in future it is expected to treat

39. 3 FUTURE PERSPECTIVE Disease- Gene of interest Company perusing gene therapy AADC deficiency (CNS) AADC PTC Therapeutics Cystic Fibrosis CTFR Vertex Congestive heart failure Adenyl cyclase 6 Renova Choroideremia CHM Spark Metachromatic leukodystrophy ARSA GlaxoSmithKline (GSK) Table of gene therapies to be persuaded in 2020

40. 42 GENE DOPING The hepothetical non-therapeutic use of  genes ,  genetic  elements or cells that have the capacity to enhance athletic performance" There are numerous genes of interest as agents for gene doping;   Present in skeletal muscles, different forms, related to power

41. 43 IMPROVING THE VECTOR

42. 44 ACCESS OF PATIEENTS TO THERAPY

43. When optimizing the efficacy of a new drug, a central challenge is the search for minimum effective dose. As companies move through Phase 1 and 2 trials , they tinker with viral load, in order to optimize exogenous protein levels in patients. As you increase the intensity of the gene therapy (viral load), you should be inserting more genetic material for the deficient protein into the necessary cells. However, an excessively high viral load can cause toxicity issues (liver damage, hyper-activated immune system). So, an  ideal gene therapy protocol will administer the minimum effective dose of virus . 45 OPTIMIZING THE EFFICACY

44. The introduction and implementation of gene therapy has opened new doors in the field of Health sciences . But implementing a safe and effective gene therapy has not been so easy due to high cost, finessing appropriate viral system, immune rejection and ethical issues. Safety is always a concern when live vector systems are used for human gene therapy the ideal expression vector for use in humans has yet to be identified. For patients to get assess to these treatments, cost effectiveness should be included in the futuristic therapies 46 CONCLUSION

45. Bender, E. (2018). Regulating the gene-therapy revolution.  Nature ,  564 , S20-S22 . Hasan , N., & Saini, S. (2014). Gene therapy: Current status and future perspectives.  therapy ,  3 , 4 . Misra, S. (2013). Human gene therapy: a brief overview of the genetic revolution. J Assoc Physicians India, 61(2), 127-133. http://geneticeducation.co.in/gene-therapy-types-vectors-viral-and-non-viral-process-applications-and-limitations/ https ://www.risingtidebio.com/what-is-gene-therapy-uses/#recent REFERENCES 47