Human beings suffer from more than 5000 different diseases caused by single gene mutations, e.g.

cystic fibrosis acatalasis, hunting tons chorea, tay sachs disease, lisch nyhan syndrome, sickle cell

anemia, mitral stenosis, hunter’s syndrome, haemophilia, several forms of muscular dystrophy etc. In

addition, many common disorders like cancer, hypertension, atherosclerosis and mental illness seem

to have genetic components.

The term gene therapy can be defined as introduction of a normal functional gene into cells, which

contain the defective allele of concerned gene with the objective of correcting a genetic disorder or an

acquired disorder. The first approach in gene therapy is: -

a) Identification of the gene that plays the key role in the development of a genetic disorder.

b) Determination of the role of its product in health and disease.

c) Isolation and cloning of the gene.

d) Development of an approach for gene therapy.

The genetic material may be transferred directly into cells within a patient, which is referred as in vivo

gene therapy or else cells may be removed from the patient and the genetic material inserted into

them, which is referred as invitro gene therapy. Apart from the two methods mentioned above there is

one more method that is ex-vivo gene therapy in which genetic material is inserted into the cells just

prior to transplanting the modified cells back into the patient.

Major disease classes under gene therapy include: -

a) Infectious diseases: – infection by a virus or bacterial pathogen

b) Cancers: – uncontrolled and enormous cell division and cell proliferation as a result of activation of

an oncogene or inactivation of a tumors suppressor gene or an apoptosis gene.

c) Inherited disorders: – genetic deficiency of an individual gene product or genetically determined in

appropriate expression of a gene.

d) Immune system disorders: – includes allergies, inflammation and also autoimmune diseases in

which immune system cells appropriately destroy body cells.

TYPES OF GENE THERAPY: –

Gene therapy may be classified into two types

1) Germ line gene therapy

2) Somatic cell gene therapy

a) Incase of germ line gene therapy germ cells that is sperms or eggs are modified by the introduction

of functional genes, which are ordinarily integrated into their genomes. Therefore the change due to

therapy is heritable and passed onto the later generations. This approach, heretically, is highly

effective in counteracting the genetic disorders. However this option is not consider, at least for the

present for application in human beings for a variety of technical and ethical reasons.

b) In the case of somatic cell gene therapy the gene is introduced only in somatic cells, especially of

those tissues in which expression of the concerned gene is critical for health. Expression of the
introduced gene relieves symptoms of the disorder, but this effect is not heritable, as it does not

involve the germ line. It is the only feasible option, and clinical trials have already started mostly for

the treatment of cancer and blood disorders.

GENERAL GENE THERAPY STRATEGIES

1) Gene augmentation therapy (GAT): -

It is done by simple addition of functional alleles has been used to treat several inherited disorders

caused by genetic deficiency of a gene product. It is also involved in transfer to cells of genes

encoding toxic compounds (suicide genes) or prodrugs (reagents which confer sensitivity to

subsequent treatment with a drug). It has been particularly applied to autosomal recessive disorders

where even modest expression levels of an introduced gene may make a substantial difference.

2) Targeted killing of specific cells: -

Artificial cell killing and immune system assisted cell killing have been popular in the treatment of

cancers. It can be done by two ways.

a) Direct cell killing: – it is possible if the inserted genes are expressed to produce a lethal toxin

(suicide genes), or a gene encoding a prodrug is inserted, conferring susceptibility to killing by a

subsequently administered drug. Alternatively selectively lytic viruses can be used.

b) Indirect cell killing: – It uses immunostimulatory genes to provoke or enhance an immune response

against the target cell.

3) Targeted mutation correction: -

The repair of a genetic defect to restore a functional allele, is the exception, technical difficulties have

meant that it is not sufficiently reliable to warrant clinical trails.

4) Targeted inhibition of gene expression: -

It is suitable for treating infectious diseases and some cancers. If disease cells display a novel gene

product or inappropriate expression of a gene a variety of different systems can be used specifically to

block the expression of a single gene at the DNA, RNA or Protein levels.

ETHICAL ISSUES REGARDING GENE THERAPY

Gene therapy is not in use because of many drawbacks. Germ line therapy is a more difficult issue.

The problem is that the techniques used for germ line correction of inherited disease are exactly the

same techniques that could be used for germ line manipulation of other inherited characteristics.

Indeed, the development of this technique with animals has not been prompted by any desire to cure

genetic diseases, the aims being to improve farm animals for example by making genetic changes that

result in low fat content. This type of manipulation, where the genetic constitution of an organism is

changed in a directed, heritable fashion, is clearly unacceptable with humans at present technical

problems mean that human germ line manipulation would be extremely difficult. Before these

problems are solved we should ensure that the desire to do good should not raise the possibility of

doing tremendous harm.

REFERENCE

1) Tom strachan and Andrew P. Read, Human Molecular Genetics, Second edition.

2) T.A. Brown, Gene Cloning an introduction, Third Edition.

3) S.N. Jogdand, Gene Biotechnology.

4) B.D Singh, Biotechnology.