genetic as medicine

Role of genetic as medicine(gene therapy)

by-Vanlalmawiarol.no-12

What is genetic disorder/ diseases caused by an abnormality in an

individual's DNA. Abnormalities can be as small as a

single-base mutation in just one gene, or they can involve the addition or

subtraction of entire chromosomes.

Types of Genetic DisordersChromosomes and

chromosome abnormalities

Addition or deletion of entire chromosomes or parts of chromosomes

example is trisomy 21 - Down syndrome

Types of Genetic DisordersSingle gene disorders Single mutant gene

has a large effect on the patient

Sickle cell anaemia - autosomal recessive

Haemophilia - X-linked

Types of Genetic DisordersPolygenic Disorders The most common yet still the least

understood of human genetic diseases Result from an interaction of multiple

genes, each with a minor effect Type I and type II diabetes, autism,

osteoarthritis

Amo

polygenic disorder - an inherited disease controlled by several genes at once.

Types of Genetic DisordersMutation and human disease Three principal types of mutation

Single-base changesDeletions/InsertionsUnstable repeat units

Two main effectsLoss of functionGain of function

What is Gene Therapy correcting defective genes that are

responsible for disease development inserting a normal gene to replace an

abnormal gene.

What’s gene therapy?Imagine that you accidentally broke one of your neighbor's windows. I. Stay silentII. Repair it with

some tapeIII. Put in a new

window

Many medical conditions result from flaws, or mutations, in one

or more of a person's genes. So, if a flawed gene caused our "broken window," can you "fix" it? What are your options?I. Stay silentII. Try to treat the disorder with

drugs or other approachesIII. Put in a normal, functioning

copy of the gene

How to fix itA

B C a beneficial geneA

virus modified virus A virus is found which replicates by inserting its genes

into the host cell's genome. This virus has three genes - A, B and C.

Gene A encodes a protein which allows this virus to insert itself into the host's genome.

Genes B and C actually cause the disease this virus is associated with.

Replace B and C with a beneficial gene. Thus, the modified virus could introduce your 'good gene' into the host cell's genome without causing any disease.

So we use the modified virus to fix the “broken window”

Gene therapy Researchers are studying gene

therapy for a number of diseases, such as Severe combined immuno-deficiencies

(SCID) Cancer HIV, etc.

HISTORY AND DEVELOPMENT OF GENE THERAPY

1960: The concepts of Gene Therapy was introduced 1970: Friedmann and Roblin author of a paper in

Science titled "Gene therapy for human genetic disease?” cite the first attempt to perform gene therapy

1990: The first approved gene therapy case at the

National Institute of Health, U.K. It was performed on a four year old girl named Ashanti DaSilva. It was a treatment for a genetic defect that left her with an immune system deficiency

Sickle cell disease is successfully treated in mice

2006: Scientists at the National Institutes of Health (Bethesda, Maryland) have successfully treated metastatic melanoma in two patients. This study constitutes one of the first demonstrations that gene therapy can be effective in treating cancer.

2007- 2011: Research is still ongoing and the number of diseases that has been treated successfully by gene therapy increases.

Retinal disease Color blindnessAdrenoleukodystrophy

2011: Medical community accepted that it can cure HIV as in 2008, Gero Hutter has cured a man from HIV using gene therapy

TYPES OF

GENE THERAP

Y

GERM LINE GENE THERAPY

SOMATIC GENE

THERAPY

GERM LINE GENE THERAPY

Result in permanent changes. Potential for offering a permanent therapeutic

effect for all who inherit the target gene. Possibility of eliminating some diseases from a

particular family. Also raises controversy: Some people view this type of therapy as

unnatural, and liken it to "playing God”. Others have concerns about the technical

aspects.

Amo

In germline gene therapy (GGT), germ cells (sperm or eggs) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations.

SOMATIC GENE THERAPY Affects only the targeted cells in the patient,

and is not passed to future generations. Short-lived because the cells of most tissues

ultimately die and are replaced by new cells. Transporting the gene to the target cells or

tissue is also problematic. Appropriate and acceptable for many

disorders, including cystic fibrosis, muscular dystrophy, cancer, and certain infectious diseases.

Amo

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any of any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring.

Types of somatic gene therapy Ex vivo

cells are modified outside the body and then transplanted back in again

called ex vivo because the cells are treated outside the body

In vivogenes are changed in

cells when the cells are still in the body

called in vivo because the gene is transferred to cells inside the patient’s body

STEPS IN GENE THERAPY:

1. Identification of the defective gene.2. Cloning of normal healthy gene.3. Identification of target cell / tissue / organ.4. Insertion of the normal functional gene into the host DNA.

METHOD: Introduction of FUNCTIONAL GENES into appropriate cells

Transferred gene (TRANSGENE) encodes & produces proteins

The Proteins encoded by Transgene corrects the disorder

METHODS OF GENE DELIVERY: 1. PHYSICAL METHODS: -Microinjection -Aerosol -Gene gun

2. CHEMICAL METHODS: -Liposomes 3. BIOLOGICAL METHODS: Viral Vectors like -Retrovirus -Adenovirus

LIPOSOMES:

These are lipid bilayers surrounding an aqueous vesicle. Can be used to introduce foreign DNA into a target cell.

Advantages: Safer when compared to Viral vectors. Can carry large DNA molecules.

Disadvantages: Inefficient transfer.

ADENO VIRUSES:

Second most commonly used delivery system in gene therapy.

Adenoviruses can be produced at high titres in cultures.

Advantages: Can infect non-dividing cells , thus suitable for gene

therapy. Efficient gene transfer.

Disadvantages:. Provokes immune response.

VARIOUS STRATEGIES in GENE THERAPY:

1. GENE AUGMENTATION THERAPY

2. TARGETED MUTATION CORRECTION

3. INHIBITION OF GENE EXPRESSION

4. GENE THERAPY TO ACHIEVE PHARMACOLOGICAL EFFECTS

1. GENE AUGMENTATION THERAPY: If a disease is caused by a mutation causing loss of

function, introduction of a FUNCTIONAL COPY OF THE GENE

into the cell will restore the normal function of the gene.

Examples:1. Deficiency of ADA2. Haemophilia

2. TARGETED MUTATION CORRECTION: Correction of mutation, by changing the mutated

nucleotide sequence to normal.

Practically difficult, but in principle can be done by homologous recombination.

3. INHIBITION OF GENE EXPRESSION

In case of mutations that have a negative dominant effect, the expression of the mutated gene can be blocked at the DNA / RNA / protein level.

Examples: This strategy is useful in Cancers caused by

inappropriate expression of a gene.

4. GENE THERAPY TO ACHIEVE PHARMACOLOGICAL EFFECTS:

Examples: 1. Introduction of a gene that makes cancer cells

susceptible to anticancer drugs. 2. Introduction of a toxic gene whose expression kills

cancer cells. 3. Genes of cytokines can be introduced into cells of

immune system to enhance their potential to kill diseased

cells.

ADVANTAGES OF GENE THERAPY Give a chance of a normal life to baby

born with genetic disease. Give hope of healthy life to cancer

patient. For certain disease that do not have any

cure except gene therapy, it could save many lives

RISKS OF GENE THERAPY:

1.Adverse reactions due to the virus or new genes.

2.Activation of proto-oncogene leading to formation of ontogeny.

3.Introduction of a mutation to the next generation.

Any question