Genetic screening & gene therapy
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Genetic screening & gene therapy Genetic screening & gene therapy Presentation Transcript

    Genetic screening &
    Gene therapy
    Dr. Dinesh T
    Junior resident,
    Department of Physiology,
    Dr sclerodinesh
  • Introduction
  • History
    Technology 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.
  • 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
  • 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.
  • Genetic screening
  • 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.
  • Genetic screening
    Genetic screening is often used to detect faulty or
    abnormal genes in an organism
    Can detect some genes related to an increasedrisk of cancer
    Can detect some genes known to cause geneticdisorders
  • 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.
  • Gene tests (also called DNA-based tests), in a broader sense
    Direct examination of the DNA molecule
    Biochemical tests for such gene products as enzymes and other proteins
    Microscopic examination of stained or fluorescent chromosomes
  • Genetic tests
    Who can order?
    What are the samples needed?
    How to interpret the tests?
    What are all the risks?
    Ethical considerations?
  • Types of screening tests
    • Carrier screening
    • Prenatal diagnostic testing
    • Newborn screening
    • 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
    • Pre implantation genetic diagnosis
    • Forensic/ identity testing
    • Research
    • Pharmacogenomics
  • Genetic screening
    Adult Polycystic Kidney Disease
    Alpha-1-antitrypsin deficiency
    Amyotrophic lateral sclerosis
    Alzheimer's disease
    Ataxia telangiectasia
    Central Core Disease
    Charcot-Marie-Tooth disease
    Congenital adrenal hyperplasia
    Cystic fibrosis
    Duchenne muscular dystrophy/Becker muscular dystrophy
    Emanuel Syndrome
    Fanconianemia, group C
    Factor V-Leiden
    Fragile X syndrome
    Gaucher disease
    Hereditary Hemochromatosis
    Huntington's disease
    Hereditary nonpolyposis colon cancer
    Hemophilia A and B
    Inherited breast and ovarian cancer
    Marfan Syndrome
    Myotonic dystrophy
    Neurofibromatosis type 1
    Polycystic Kidney Disease
    PraderWilli/Angelman syndromes
    Sickle cell disease
    Spinocerebellar ataxia, type
    Spinal muscular atrophy
    Tay-Sachs Disease
    Timothy Syndrome Galactosemia
  • Methods for prenatal screening
  • Indications for prenatal diagnosis
    • Abnormal results in prenatal screening
    • Previous child with a chromosome abnormality
    (probability of translocation carrier in parents)
    • Family history of a chromosome abnormality
    • Family history of a single gene disorder
    • Family history of neural tube defect or other
    congenital abnormalities
  • Newborn Screening Tests:
    Maple Syrup Urine Disease
    Congenital Adrenal Hyperplasia
    Congenital Hypothyroidism
    Biotinidase Deficiency
    Phylketonuria (PKU)
    Sickle cell and Other Hemoglobinopathies
  • 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.
  • Pros and cones of gene testing
    • To clarify a diagnosis and direct a physician
    • To avoid having children with devastating diseases
    • Identify people at high risk
    • Provide doctors with a simple diagnostic test
    • Transforming it from a usually fatal condition to a treatable one
    • Possibility of laboratory errors
    • Potential for provoking anxiety, and risks for discrimination
    social stigmatization could outweigh the benefits of testing
  • Genetic counseling
  • 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,
    • 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)
    • During childhood (i.e. if the child has developmental
    • During adulthood (for adult onset genetic conditions
    such as Huntington’s disease or hereditary cancer
    • The couple should be counselled by a genetic counsellor to inform them of the test results and the risks to the foetus.
    • Providing the options open to them in management and family planning in order to prevent, avoid or ameliorate it.
    • Autonomy of decision is crucial.
    • 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
    • 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.
  • Gene therapy
  • Gene therapy is the replacement of faulty genes.
    Introduction of functional
    genetic material into target
    cells to replace or
    supplement defective
    genes, or to modify target
    cells so as to achieve
    therapeutic goals.
  • 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).
    • All gene therapy so far in people has been directed at somatic cells.
    • 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
  • Somatic Cell Therapy
    This is when a gene is introduced into a
    patient to help them recover from a
  • Germ Line Therapy
    Changes are made to genes that will affect
    subsequent generations.
  • Applications of Gene Therapy
    Radical 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.
  • Gene therapy concerns
  • Vectors in gene therapy:
    Non-viral methods
    Adeno-associated viruses
    Hybrid methods
    Lipoplexes and polyplexes
    Naked DNA
    Envelope protein pseudotyping of viral vectors
  • 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.
  • Non viral vectors
    Un complexed plasmid DNA
    DNA coated gold particles
    DNA – protein conjugates
  • Modes of introducing genetic material
  • Un complexed Plasmid DNA
    Purified 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.
  • DNA coated Gold particles
    • Plasmid DNA + Gold particles ( 1 micron india)
    • “shot” into cells using electric spark or
    pressurized gas – “gene gun”
    • Epidermis
    • Skin tumours (melanomas)
    • Gene mediated immunization
  • Liposomes
    • 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
  • DNA- Protein conjugates
    • Cell- specific DNA delivery systems
    • Utilize unique cell surface receptors on
    target cells
    • Chemical cross linking methods used
  • 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
    • The regulation (the degree to which a gene is turned on or off)
    of a particular gene could be altered.
  • Gene Transfer techniques
    • In vivo
    Suspension containing vector is injected
    directly into the patient either systemically (i.v.)
    or directly into target tissue (e.g. malignant
    • Ex vivo
    Target cells (stem cells,myoblasts,fibroblasts
    etc) removed from the patient, treated with
    vector and injected back into the patient
  • Spectrum of gene expression
    Gene replacement for single gene disorders
    Gene repair
    Gene inactivation
    Ectopic synthesis of therapeutic proteins
    Cancer gene therapy
  • A) Immunodeficiency Disorders
    Adenosine Deaminase Deficiency
    X- linked SCID
    Chronic Granulomatous disease
    B) Liver Disease
    Familial Hypercholesterolemia
    Haemophilia A
    Target diseases
  • Hemoglobinopathies
    D) Lung Diseases
    • Cystic Fibrosis
    • α- 1 Antitrypsin Deficiency
    E) Skeletal Muscle
    • Duchene Muscular Dystrophy
    • Limb Girdle Muscular Dystrophy
  • Challenges
    • Short-lived nature of gene therapy
    • Difficult to treat multi gene or multi factorial disease
    • Inserting gene into correct cells.
    • Controlling gene expression. Possibility of over expression
    • Damage to the host gene
    • Acquirement of virulence
    • Chance of inducing a tumour (insertional mutagenesis)
  • Conclusion
  • Thank u all….