Advancements of medical biotechnology in gene therapy


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Gene therapy refers to the insertion of genetic material to correct a genetic defect.
In gene therapy, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene

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  • Advancements of medical biotechnology in gene therapy

    1. 1. Advancements of MedicalBiotechnology in Gene Therapy Presented by Dr. B. Victor., Ph. D Email : Blog:
    2. 2. Presentation outline Human genetic disorders-types, features. Gene therapy- definition, kinds and history. Somatic cell and Germ line gene therapy Ex vivo and In vivo gene therapy Gene delivery vectors: Viral and Non-viral vectors. Gene targeting Naked DNA gene therapy, post-natal gene therapy and pre-natal gene therapy Risks and recent developments. Conclusion
    3. 3. Human genetic disorders
    4. 4. Kinds of human geneticdisorders
    5. 5. DNA / gene mutation
    6. 6. Functional ornon-functional DNA Genes are sequences of bases. Genes replicate exactly. Gene is transcribed into mRNA. mRNA is translated into Protein. Proteins do metabolic functions. Mutated genes are non- functional (build wrong, interact wrong). Mutated genes are inherited; result is genetic disease.
    7. 7. Basis of genetic disorder
    8. 8. What is a genetic disorder?
    9. 9. What is gene therapy?
    10. 10. Concepts of gene therapy techniques Replacement of a abnormal gene with normal gene. Repairing the abnormal gene. Altering how that gene is controlled. Get other cells to take over function of abnormal cells. Inserting correct protein and bypass gene function.
    11. 11. Kinds of Gene Therapytechniques
    12. 12. Technique of genetherapy
    13. 13. Gene therapy :mechanism
    14. 14. Steps in gene therapytechnology
    15. 15. Different genetic diseases need different genetherapy approaches
    16. 16. History of gene therapy :In the beginning…◦ In the 1980s, Scientists inserted human genes into a bacteria cell.◦ Then the bacteria cell transcribed and translated the information into a protein.◦ Then they introduced the protein into human cells.
    17. 17. The First gene therapy case wasperformed on September 14th,1990.  Ashanti De Silva was treated for SCID(Sever combined immunodeficiency).  Doctors removed her white blood cells, inserted the missing gene into the WBC, and then put them back into her blood stream.  This strengthened her immune system  This only worked for a few months.
    18. 18. 9/17/1999Jesse Gelsinger, 18 years high school graduate with OTC deficiency, died participating in a gene therapy experiment at theUniversity of Pennsylvania in Philadelphia,
    19. 19. The first gene therapy cure  2000 - The first gene therapy cure was reported when Alain Fischer (Paris) succeeded in totally correcting children with SCID-X1, or “bubble boy” syndrome
    20. 20. Flow chart showinggene therapy types
    21. 21. Types of gene therapy;Germ line gene therapy: Healthy gene is introduced into reproductive cells E.g., eggs, sperms.Somatic cell gene therapy: Healthy gene is introduced into adult somatic cells(body cells). E.g., bone marrow cells, hepatic cells, central nervous system cells. Gene addition therapy : Functional gene is introduced into the somatic cell in addition to defective gene endogenous to the cell. Gene targeting : Inactivate a functional defective endogenous gene.
    22. 22. ex vivo(in vitro) and in vivo somatic gene therapyEx vivo gene therapy- refers to the transfer of genes in cultured cells (outside the body) (e.g., bone marrow cells) which are then reintroduced into the patient. This technique is used for treating genetic diseases of blood system.In vivo gene therapy- the direct delivery of genes into the cells of a particular tissue. This technique is used for treating tissue – based genetic diseases e.g., Duchenne muscular dystrophy (DMD).
    23. 23. Steps in somatic cellgene therapy
    24. 24. Human ex vivo gene therapy
    25. 25. Gene targeting ortargeted gene transfer It is a form of in-vivo site directed mutagenesis involving homologous recombination between a targeting vector containing one allele and an endogenous gene represented by a different allele. Gene targeting can be used either to inactivate a functional endogenous gene or to correct a defective gene. The first case ( in 1985) was used to disrupt the human b-globin gene in cultured cells.
    26. 26. Problems with ex-vivo methodof gene Therapy Problems Risks Not enough cells Cells injected may get desired gene cause an immune to correct response problem Random insertion of Modified cells retrovirus into host don’t last long; chromosome- may need repeat likely to interrupt the treatments coding DNA.
    27. 27. Gene delivery viral VectorsAdenovirusesRetrovirusesAdeno-Associated Viruses (AAV)Herpes simplex viruses
    28. 28. Choices of gene delivery Vectors Viral vectors: Retrovirus Adenovirus Adeno-associated virus Herpes Simplex Virus Non-viral vectors: Liposome DNA–polymer conjugates Naked DNA
    29. 29. Characteristics of ideal genedelivery vector system an adequate carrying capacity. to be undetectable by the immune system. to be non-inflammatory. to be safe to the patients with pre-existing lung inflammation. to have an efficiency sufficient to correct the genetic disease. to have long duration of expression.
    30. 30. Adenovirus(non-specific insertion) Adenoviruses have double- stranded DNA genomes. Adenoviruses cause respiratory, intestinal, and eye infections in humans. The common cold is caused by an adenovirus. Adenovirus genome can accept large insertions of human DNA. Penetration into the cell is by endocytosis. The viral core migrates to the nucleus where the DNA enters through nuclear pores and becomes incorporated into the genome.
    31. 31. Retrovirus (non-specific insertion): Retroviruses are group of RNA viruses. Retroviruses contain two copies of the genome in each viral particle. Human immunodeficiency virus (HIV) is a retrovirus. On infection the ssRNA is converted into dsDNA copy by reverse transcriptase and is integrated into the host cell genome by a viral integrase enzyme.
    32. 32. Adeno-Associated Virus (specific insertion) A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19. Penetration and Gene Transfer mechanisms are similar to the Adenovirus. Several genetic disorders are related to genes on chromosome 19 (70 known genetic disorders): for example:  Alzheimer’s disease  Leukemia  Muscular Dystrophy  Congenital Hypothyroidism  Several Cancers (ovarian, colorectal, etc.)
    33. 33. Herpes simplex viruses A class of dsDNA viruses that infect a neurons. It has a 150 kbp dsDNA genome. It consists of over 70 genes.e.g., Cold sores virus
    34. 34. Non-viral DNA carriers:Cationic liposomes Positively charged lipids interact with negatively charged DNA. (lipid-DNA complex).The liposome carries the therapeutic DNA through the target cell membrane. Advantages: a. Stable complex b. Can carry large sized DNA c. Can target to specific cells d. Does not induce immunological reactions. Disadvantages: a. Low transfection efficiency b. Transient expression c. Inhibited by serum d. Some cell toxicity
    35. 35. Naked DNA gene therapy ◦ Intramuscular and Intravascular delivery (liver and muscle). ◦ covalently closed circular form is more stable that open plasmid ◦ Results in a prolonged low level expression in vivo ◦ Very cheap ◦ DNA vaccines based on naked DNA are unaffected by pre-existing immunity e.g. due to maternal antibodies
    36. 36. Postnatal Gene Therapy Correction of the deleterious effects of genetic disease via long term integration of gene sequences into a patient’s genome. This property makes the use of retroviral vectors particularly attractive when considering effective gene delivery to correct inherited monogenetic disorders.
    37. 37. Types of Postnatal Gene Therapy Gene replacement: non-functional or defective gene is replaced by a new, functional copy of the gene.  Can be accomplished by homologous recombination. Gene addition: introduction of a gene that is able to produce a protein not normally expressed in the cell.  i.e. Introduction of a so-called “suicide gene” into cancer cells
    38. 38. Prenatal or in utero gene therapyTargets genetic diseases which require lifelong correctionThe concept of fetal gene therapy is based on the following aims: avoiding early-onset manifestation of life- threatening genetic conditions achieving permanent correction of such diseases by stable transduction. Avoiding immune reactions against the therapeutic vector and transgene.
    39. 39. Prenatal gene therapy
    40. 40. Benefits of prenatal gene therapyProvides early phenotypic correction of genetic disease.Demonstration of long-term postnatal therapeutic protein production.Tolerance to the transgenic protein can be induced by in utero expression.
    41. 41. Risks of Gene Therapy New gene might be inserted into wrong location in the DNA (misfire). Other genes may be accidentally delivered to the cell. The deactivated vector virus may be contagious. The viral vectors cause toxicity and inflammatory responses. The vector viruses can infect more than one type of cell. Over-expression of missing protein. Immune system complications.
    42. 42. Recent Developments Genes get into brain using liposomes coated in polymer call polyethylene glycol  potential for treating Parkinson’s disease RNA interference or gene silencing to treat Huntington’s  siRNAs used to degrade RNA of particular sequence  abnormal protein wont be produced Create tiny liposomes that can carry therapeutic DNA through pores of nuclear membrane Sickle cell successfully treated in mice
    43. 43.  Dr.B.Victor is a highly experienced professor, recently retired from the reputed educational institution- St. Xavier’ s College, Palayamkottai, India-627001. He was the dean of sciences, IQAC coordinator and assistant controller of examinations. He has more than 32 years of teaching and research experience He has taught a diversity of courses and guided 12 Ph.D scholars. send your comments to :