This document discusses the history and current state of genetic screening, genetic counseling, and gene therapy. It provides a timeline of major developments in these fields from 1961 to 2008. Key points include the first approved gene therapy case in 1990, the first gene therapy treatment for ADA deficiency in 2002, and over 1,200 genetic tests being available by 2008. The document also describes various genetic screening tests, the role of genetic counseling, methods of genetic screening and gene therapy delivery, as well as challenges and applications of these emerging fields.

1. Genetic screening &
Gene therapy
Dr. Dinesh T
Junior resident,
Department of Physiology,
JIPMER
Dr sclero dinesh

2. Introduction

3. Genetic
screening
Counseling
Gene
therapy

4. 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.

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 screening
 Genetic screening is often used to detect faulty or
abnormal genes in an organism
 Can detect some genes related to an increased
risk of cancer
 Can detect some genes known to cause genetic
disorders

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 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

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
• 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

15. 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
 Dystonia
 Emanuel Syndrome
 Fanconi anemia, 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
 Mucopolysaccharidosi
 Myotonic dystrophy
 Neurofibromatosis type 1
 Phenylketonuria
 Polycystic Kidney Disease
 Prader Willi/Angelman syndromes
 Sickle cell disease
 Spinocerebellar ataxia, type
 Spinal muscular atrophy
 Tay-Sachs Disease
 Thalassemias
 Timothy Syndrome Galactosemia

16. Methods for prenatal screening
Pre natal
screening
Invasive
Amniocentesis Chorionic villous
biopsy
Fetal blood
sampling
from maternal
blood
Non invasive
Ultra
sonogram
Maternal serum
markers
Pre
implantation

17. 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

18. Newborn Screening Tests:
 Maple Syrup Urine Disease
 Congenital Adrenal Hyperplasia
 Congenital Hypothyroidism
 Glactosemia
 Biotinidase Deficiency
 Homocystinuria
 Phylketonuria (PKU)
 Sickle cell and Other
Hemoglobinopathies

19. 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.

20. 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

21. Genetic counseling

22. 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.

23. 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
delay)
• During adulthood (for adult onset genetic conditions
such as Huntington’s disease or hereditary cancer
syndromes).

24. •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.

25. 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.

26. Gene therapy

27. 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.

28. 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).

29. • All gene therapy so far in people has been
directed at somatic cells.
• Germ line engineering in humans remains only a
highly controversial prospect.

30. 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

31. Somatic Cell Therapy
This is when a gene is introduced into a
patient to help them recover from a
disease.

32. Germ Line Therapy
Changes are made to genes that will affect
subsequent generations.

33. 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.

34. Gene therapy concerns

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

37. 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.

38. Non viral vectors
 Un complexed plasmid DNA
 DNA coated gold particles
 Liposomes
 DNA – protein conjugates

39. Modes of introducing genetic material
Modes
Physical
methods
Gene gun
Sonoporation
Electroporation
Hybrid methods
Chemical
methods
Oligonucleotides
Lipoplexes
Dentrimers

40. 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.

41. 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

42. 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

43. DNA- Protein conjugates
 • Cell- specific DNA delivery systems
 • Utilize unique cell surface receptors on
 target cells
 • Chemical cross linking methods used

44. 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.

45. 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
tumour)
• Ex vivo
Target cells (stem cells,myoblasts,fibroblasts
etc) removed from the patient, treated with
vector and injected back into the patient

49. Spectrum of gene expression
 Gene replacement for single gene disorders
 Gene repair
 Gene inactivation
 Ectopic synthesis of therapeutic proteins
 Cancer gene therapy

50. A) Immunodeficiency Disorders
 Adenosine Deaminase Deficiency
 X- linked SCID
 Chronic Granulomatous disease
B) Liver Disease
 Familial Hypercholesterolemia
 Haemophilia A
Target diseases

51.  Hemoglobinopathies
 D) Lung Diseases
• Cystic Fibrosis
• α- 1 Antitrypsin Deficiency
 E) Skeletal Muscle
• Duchene Muscular Dystrophy
• Limb Girdle Muscular Dystrophy

52. 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)

53. Conclusion

54. Thank u all….