15 Therapy Of Genetics Diseases

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15 Therapy Of Genetics Diseases

  1. 1. Therapy of Genetic Diseases Weiying Jiang Department of medical genetics
  2. 2. Gene Therapy Conventional Approaches Therapy of Genetic Diseases
  3. 3. Dietary Therapy Protein and Enzyme replacement Pharmacal Therapy Surgery Conventional Approaches
  4. 4. Dietary Therapy
  5. 5. Protein and Enzyme replacement Hemophilia Factor Ⅷ Replacement
  6. 6. Protein and Enzyme replacement Enzymatic Therapy β-glucosidase β-glucosidase Gaucher disease Lysosome
  7. 7. Pharmacal Therapy Prenatal Therapy
  8. 8. Patient Therapy Substitution Addition Remove surplus Vitamine
  9. 9. Substitution Dwarf Growth hormone
  10. 10. Remove surplus sodium dimercaptosulphonate , (DMPS) Cu ++ Wilson’s Disease
  11. 11. Remove surplus Statins Lower cholesterol LDL receptor Increased LDL clearance form plasma Inhibiting HMG-CoA reducease
  12. 12. Blood filter Familial hypercholesterolemia heparin agarose Ca2Cl
  13. 13. Surgery Orthopedics Cleft lip
  14. 14. Presymptom Therapy Familial polyposis coli.
  15. 15. Transplantation
  16. 16. Therapeutic applications of recombinant DNA Technology Pig pancreas Insulin
  17. 17. Therapeutic applications of recombinant DNA Technology
  18. 18. Insulin
  19. 19. Gene Therapy The deliberate introduction of genetic material into human somatic cells for therapeutic, prophylactic or diagnostic purposes.
  20. 20. Protocols of Gene therapy Somatic versus Germline Gene therapy Ex vivo versus in vivo Gene therapy
  21. 21. Somatic Cell Gene therapy Manipulating the genome of somatic cells in selected tissues .The effect of the therapy are planned to be limited to the individual undergoing treatment and are not designed to introduce potentially heritable genetics modification.
  22. 22. Germline Gene therapy It is possible to permanently modify the germline of animals,which makes the young generation normally .In theory, it should be possible to do in people.
  23. 23. Transfer of the target DNA Physical Method Chemical Method Membrane integration Virus vector Receptor system Homo-recombination
  24. 24. Physical Method Injection
  25. 25. Electroporation DNA
  26. 26. DNA DNA
  27. 27. Micro-particle Bombardment Micro -particle of Gold or Wolfram DNA
  28. 28. Gene Gun Very high speed
  29. 30. Membrane integration lipisome delivery system A lipisome is an ambipathic molecular capable of binding to DNA and incorporating it into a lipid bilayer which facilitates endocytic entry of the DNA into cells. p346
  30. 31. lipid bilayer Cationic DNA-lipid complex
  31. 32. Virus Vector The process of using a virus to carry a foreign gene into a cell is referring to as transduction.
  32. 33. Virus Vector Retrovirus Lentivirus Adenovirus Adeno-Associated Virus Herpesvirus
  33. 35. 5‘ 3’ LTR gag pol env LTR U3 R U5 U3 R U5 ψ Mo-MLV Structure (Moloney-Murine Leukemia Virus)
  34. 36. 5’ 3’ U3 R U5 U3 R U5 ψ Target DNA Replication Defective- Virus U3 R U5 U3 R U5 gag pol env Help virus
  35. 37. Approaches of Gene therapy
  36. 38. Ex vivo Gene therapy (p344) The cells to be modified are first removed from the patient genetically modified in tissue culture, then returned to the patient. Approaches of Gene therapy
  37. 39. DNA recombination
  38. 40. In vivo Gene therapy Attempt to treat the patient with a gene delivery vehicle that will transfer the target gene to the appropriate target organ and directly modify the genome of the target cells.
  39. 42. Gene Therapy Strategies RNA modification Target gene correction Somatic stem-cell therapy Embryonic stem-cell therapy
  40. 43. RNA modification Ribozymes RNAi Antisense Technology
  41. 44. Regulation of gene expression— Antisense Technology A method for negating gene expression involves in the introduction of a single strand DNA, RNA or even synthetic nucleic acid derivative that is complementary to the sequence of the target gene. The complementary antisense nucleic acid can then bind to the single mRNA translated from the targeted gene to create a double strand molecule that is no longer able to translate.
  42. 45. DNA Antisense DNA transcription RNA Sense Strand
  43. 46. RNA Antisense RNA
  44. 47. Human β-globin E1 E2 E3 Intron1 Intron2 GT AG
  45. 48. Human β-Globin IVS-2 654(C T) 突变 E1 E2 E3 Intron1 Intron2 GT AG GT AG GT AG
  46. 49. Human β-Globin IVS-2 654(C T) 突变 E1 E2 E3 Intron1 Intron2 GT AG GT GT AG
  47. 50. Human β-globin E1 E2 E3 Intron1 Intron2 GT AG
  48. 51. Ribozymes RNA digestion transcription blocked
  49. 52. RNA interference, RNAi Andrew Fir Craig mello
  50. 53. RNA interference (RNAi ) RNAi silencing is triggered by double-stranded RNA .
  51. 55. Artificial generation of dsRNA from a hairpin construct
  52. 57. Double DNA siRNAs RNA-induced silencing complex (RISC ) Containing targets cognate mRNAs for inactivation Dicer
  53. 58. In situ repair: 5’ATCGGG T CAATTCGA3’ mutation 3’TAGCCA A GTTAACGA5’ 5’ATCGGG G CAATTCGA3’ wild 3’TAGCCA C GTTAACGA5’ Target gene correction
  54. 59. Stem-cells transplantation
  55. 60. Stem-cells transplantation Stem cells are unspecialized cells that defined by their capacity for self-renewal and the ability to differentiate into the cell types found in the tissue which they are derived.
  56. 61. Stem-cells transplantation
  57. 62. Somatic stem-cells transplantation Bone marrow transplantation Risk of infection Graft-versus host disease Limit donors Disadvantage
  58. 63. Gene therapy using embryonic stem cells
  59. 64. Goodbye! 中山大学中山医学院医学遗传学教研室 蒋玮莹

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