Genetic screening and gene therapy can detect and treat genetic disorders. Genetic screening techniques like carrier screening, newborn screening, and prenatal diagnosis identify genetic risks. Gene therapy aims to treat diseases by replacing faulty genes, such as inserting functional genes into somatic cells. While promising, gene therapy faces challenges like safety concerns over viral vectors and ensuring proper expression of inserted genes. Genetic counseling educates patients on genetic risks and testing options.

1. GENETIC SCREENING & GENE THERAPYGenetic screening & Gene therapyDr. Dinesh TJunior resident,Department of Physiology, JIPMERDr sclerodinesh

2. Introduction

4. HistoryTechnology to detect and treat inborn diseases - 1961. 1972 Friedmann and Roblin authored a paper in Science titled "Gene therapy for human genetic disease?“The late 1980's, an international team of scientists began the project to map the human genome.September 14, 1990 - first approved gene therapy case in the United States took place.

5. 1992 - Doctor Claudio Bordignon, Milan, Italy performed the first procedure of gene therapy using hematopoietic stem cells.1995 DNA testing in forensic cases gains fame in the O.J. Simpson trial. 2002 - first successful gene therapy treatment for adenosine deaminase-deficiency (SCID)2003 – at University of California, Los Angeles research team inserted genes into the brain using liposome coated in a polymer called polyethylene glycol

6. 2006 - Preston Nix from the University of Pennsylvania School of Medicine reported on VRX496, a gene-based immunotherapy for the treatment of human immunodeficiency virus (HIV) that uses a lentiviral vector for delivery of an antisense gene against the HIV envelope 2007 – Moorfields Eye Hospital and University College London's Institute of Ophthalmology announced the world's first gene therapy trial for inherited retinal disease 2008 there were more than 1,200 clinically applicable genetic tests available.

7. Genetic screening

8. What is genetic screening?The newest and most sophisticated of the techniques used to test for genetic disorders. One of the fastest moving fields in medical science.A technique to determine the genotype or phenotype of an organism.Determines risk of having or passing on a genetic disorder.

9. Genetic screeningGenetic screening is often used to detect faulty or abnormal genes in an organismCan detect some genes related to an increasedrisk of cancerCan detect some genes known to cause geneticdisorders

10. Genetic tests The analysis of chromosomes (DNA), proteins, and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes, or karyotype for clinical purposes.

11. Gene tests (also called DNA-based tests), in a broader senseDirect examination of the DNA molecule Biochemical tests for such gene products as enzymes and other proteinsMicroscopic examination of stained or fluorescent chromosomes

12. Genetic tests Who can order?What are the samples needed?How to interpret the tests?What are all the risks?Ethical considerations?

13. Types of screening tests Carrier screening

14. Prenatal diagnostic testing

15. Newborn screening

16. Pre symptomatic testing for predicting adult-onset disorders such as Huntington's disease Pre symptomatic testing for estimating the risk of developing Adult-onset cancers and Alzheimer's disease. Conformational diagnosis of a symptomatic individual

17. Pre implantation genetic diagnosis

18. Forensic/ identity testing

19. Research

20. Pharmacogenomics

21. Genetic screeningAdult Polycystic Kidney Disease Alpha-1-antitrypsin deficiency Amyotrophic lateral sclerosis Alzheimer's diseaseAtaxia telangiectasiaCentral Core DiseaseCharcot-Marie-Tooth diseaseCongenital adrenal hyperplasia Cystic fibrosis Duchenne muscular dystrophy/Becker muscular dystrophy DystoniaEmanuel SyndromeFanconianemia, group C Factor V-Leiden Fragile X syndrome Gaucher disease Hereditary HemochromatosisHuntington's disease Hereditary nonpolyposis colon cancerHemophilia A and B Inherited breast and ovarian cancerMarfan SyndromeMucopolysaccharidosiMyotonic dystrophy Neurofibromatosis type 1 PhenylketonuriaPolycystic Kidney DiseasePraderWilli/Angelman syndromes Sickle cell disease Spinocerebellar ataxia, type Spinal muscular atrophy Tay-Sachs Disease ThalassemiasTimothy Syndrome Galactosemia

22. Methods for prenatal screening

23. Indications for prenatal diagnosis Abnormal results in prenatal screening

24. Previous child with a chromosome abnormality (probability of translocation carrier in parents) Family history of a chromosome abnormality

25. Family history of a single gene disorder

26. Family history of neural tube defect or other congenital abnormalities

27. Newborn Screening Tests:Maple Syrup Urine DiseaseCongenital Adrenal HyperplasiaCongenital HypothyroidismGlactosemiaBiotinidase DeficiencyHomocystinuriaPhylketonuria (PKU)Sickle cell and Other Hemoglobinopathies

28. Pre implantation Genetic Diagnosis (PGD)Pre implantation Genetic Diagnosis (PGD) uses in vitro fertilisation (IVF) to create embryos.Tests one or two cells from each embryo for a specific genetic abnormality.Identifies unaffected embryos for transfer to the uterus.The approach through PGD assists couples at risk of an inherited disorder to avoid the birth of an affected child without going through selective pregnancy termination.

29. Pros and cones of gene testing To clarify a diagnosis and direct a physician

30. To avoid having children with devastating diseases

31. Identify people at high risk

32. Provide doctors with a simple diagnostic test

33. Transforming it from a usually fatal condition to a treatable one

34. Possibility of laboratory errors

35. Potential for provoking anxiety, and risks for discrimination social stigmatization could outweigh the benefits of testing

36. Genetic counseling

37. Genetic counseling The process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it,

38. This complex process can be seen from diagnostic (the actual estimation of risk) and supportive aspects. When can we do counseling? Conception (i.e. when one or two of the parents are carriers of a certain trait)During pregnancy (i.e. if an abnormality is noted on an ultrasound or if the woman will be over 35 at delivery)After birth (if a birth defect is seen)

39. During childhood (i.e. if the child has developmental delay)During adulthood (for adult onset genetic conditions such as Huntington’s disease or hereditary cancer syndromes).

40. The couple should be counselled by a genetic counsellor to inform them of the test results and the risks to the foetus.

41. Providing the options open to them in management and family planning in order to prevent, avoid or ameliorate it.

42. Autonomy of decision is crucial.

43. The ethical, legal, and religious issues should be respected.Direct-to-Consumer (DTC) genetic testing A type of genetic test that is accessible directly to the consumer without having to go through a health care professional. A variety of DTC tests, ranging from testing for breast cancer alleles to mutations linked to cystic fibrosis. Benefits of DTC testing are the accessibility of tests to consumers, promotion of proactive healthcare and the privacy of genetic information.Risks of DTC testing are the lack of governmental regulation and the potential misinterpretation of genetic information.

44. Gene therapy

45. Gene therapy is the replacement of faulty genes.Introduction of functional genetic material into targetcells to replace or supplement defective genes, or to modify target cells so as to achieve therapeutic goals.

46. In theory it is possible to transform either somatic cells (most cells of the body) or cells of the germ line (such as sperm cells,ova, and their stem cell precursors).

47. All gene therapy so far in people has been directed at somatic cells.

48. Germ line engineering in humans remains only a highly controversial prospect. For the introduced gene to be transmitted normally to offspring, it needs not only to be inserted into the cell, but also to be incorporated into the chromosomes by genetic recombination

49. Somatic Cell TherapyThis is when a gene is introduced into apatient to help them recover from a disease.

50. Germ Line TherapyChanges are made to genes that will affect subsequent generations.

51. Applications of Gene TherapyRadical cure of single gene diseases e.g. cystic fibrosis, haemoglobinopathies.Amelioration of diseases with or without a genetic component e.g. malignancies, neurodegenerative diseases, infectious diseases.

52. Gene therapy concerns

53. Vectors in gene therapy:Non-viral methods Viruses Adeno-associated viruses Retroviruses Oligonucleotides Hybrid methods Lipoplexes and polyplexesAdenoviruses Naked DNA Envelope protein pseudotyping of viral vectors

55. Gene therapy using an adenovirus vector.A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.

56. Non viral vectorsUn complexed plasmid DNA DNA coated gold particlesLiposomesDNA – protein conjugates

57. Modes of introducing genetic material

58. Un complexed Plasmid DNAPurified DNA or mRNA injected directly into tissues Injected into muscle and skin• Utility in immunization/ vaccination against Infectious diseases • Ectopic synthesis of therapeutic proteins as erythropoietin.

59. DNA coated Gold particles Plasmid DNA + Gold particles ( 1 micron india)

60. “shot” into cells using electric spark or pressurized gas – “gene gun” Epidermis

61. Skin tumours (melanomas)

62. Gene mediated immunizationLiposomes• DNA surrounded by hydrophobic molecules• Anionic – given i.v. Targets reticuloendothelial cells of liver• Cationic – transgene expression in most tissues if given in afferent blood supply• Intra airway injection or aerosol to target -lung epithelium

63. DNA- Protein conjugates• Cell- specific DNA delivery systems• Utilize unique cell surface receptors ontarget cells• Chemical cross linking methods used

64. Methods A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. An abnormal gene could be swapped for a normal gene through homologous recombination. The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.

65. Gene Transfer techniques• In vivoSuspension containing vector is injecteddirectly into the patient either systemically (i.v.)or directly into target tissue (e.g. malignanttumour)• Ex vivoTarget cells (stem cells,myoblasts,fibroblastsetc) removed from the patient, treated withvector and injected back into the patient

69. Spectrum of gene expressionGene replacement for single gene disordersGene repairGene inactivationEctopic synthesis of therapeutic proteinsCancer gene therapy

70. A) Immunodeficiency Disorders Adenosine Deaminase Deficiency X- linked SCID Chronic Granulomatous diseaseB) Liver DiseaseFamilial HypercholesterolemiaHaemophilia ATarget diseases

71. HemoglobinopathiesD) Lung Diseases • Cystic Fibrosis• α- 1 Antitrypsin DeficiencyE) Skeletal Muscle • Duchene Muscular Dystrophy • Limb Girdle Muscular Dystrophy

72. ChallengesShort-lived nature of gene therapy

73. Difficult to treat multi gene or multi factorial disease

74. Inserting gene into correct cells.

75. Controlling gene expression. Possibility of over expression

76. Damage to the host gene

77. Acquirement of virulence

78. Chance of inducing a tumour (insertional mutagenesis) Conclusion

79. Thank u all….