Gene therapy - An Introduction

What are Genes?
Genes are the basic units of life which, carry the genetic information from one generation to another. Gene therapy, as the name suggests is a therapeutic method where certain changes are carried at the genetic level of an individual. It may involve insertion of a new gene, removal of a deleterious gene or just an alteration of the gene in question. This is a relatively novel and expanding field of biotechnology which aims to treat genetic diseases in individuals.

What are Genetic diseases?
Genes are definite sequences of nucleotide bases which direct proteins synthesis in an individual including the nature and the amount of the protein to be synthesized. Each protein has a unique code carried on the gene. In case of an individual having a defective gene, the result is either absence of a certain protein or production of a faulty or abnormal protein in relation to the nature and amount of the protein in question. This is the basis of "genetic disorders".
The consequences of Genetic disorders can range from mild to severe and debilitating diseases. Some examples of genetic diseases are cystic fibrosis, muscular dystrophy, hemophilia and sickle cell anemia, etc.

The Basis of Gene therapy:
Gene therapy aims at rectifying the defective genes causing genetic diseases. The basic techniques used are:
 Replacing the defective gene by insertion of a normal gene in unspecified loci or by exchanging the gene in question by a normal gene by recombination techniques.
 Repairing the defective gene using appropriate methods like removing the gene using restriction endonucleases, or by reverting it back to normalcy by reverse mutation.
 Modifying the regulatory mechanism or the operons of the gene so as to gain control over its production.

Types of gene therapy

Basically gene therapy can be divide into two kinds
A.) Germ line gene therapy:
Here gene therapy is applied to germ cells (sperm or eggs) and the altered gene is passed on to their next generations. This being a novel approach is still under research and not used in humans as yet.

B.)Somatic gene therapy
Here gene therapy is applied to somatic cells of the host and thus the altered gene is restricted to the individual only, and not passed down the generations. This method is considered safer for humans.

Techniques involved in gene therapy:
Gene therapy involves a series of strategic techniques:

1. Isolation and Analysis of gene of interest:
The gene of interest is isolated and then analyzed using techniques of chemical or physical methods of genetic mapping to pin point the defective gene to the level of its nucleotide bases.
2. Construction of the normal gene:

Once the defective gene is found and analyzed a gene with the normal nucleotide is constructed artificially.

3. Transport of the gene construct into host cell:Basically the construct can be either transferred into the host cell as naked DNA via physical methods like electroporation, or via vectors.

4. Integrtaion of the therapeutic gene into the host cell.Naked DNA
Here the gene construct is transferred to the host cell using physical aids methods like. Some examples are Electroporation where the gene is transferred across the host cell membrane using shots of electric current or Gene gun where the DNA is shot into the host cell using high pressure.


Vectors mean "vehicles or means of transport". In the context of gene therapy, vectors are those vehicles which carry the corrected gene construct into the host cell and help in the integration of the construct into the host cell genome.

Viruses are the best vectors as by virtue of nature they integrate their DNAinto the host's genome. Then the viral DNA is also replicated along with hosts' replication cycle, thereafter. In gene therapy the gene construct is thus carried to the host cell as part of the viral DNA and easily integrated into host cell.

Now the host cell keeps producing copies of the "gene of interest" along with its each replication cycle thus leading to a large copy number of the gene which then directs the synthesis of the "corrected' protein in the host.

Examples of viruses used in Gene therapy
Retroviruses (Viruses with RNA as their genetic material)

Retroviruses produce the enzyme reverse transcriptase which makes a copy of DNA from its RNA and then integrates the DNA the host cell genome with the help of the enzyme integrase.
One successful application of retroviral vectors is the treatment of X-linked Severe combined immunodeficiency(X-SCID).

Adeno and Adeno-Associated viruses
Adenoviruses have double-stranded DNA as their genome. They have been employed in cancer treatment with a good rate of success.

Adeno-associated viruses belonging to the Parvovirus family have single stranded DNA and are still being studied for their role as vectors in gene therapy.

Applications of gene therapy:
In 1972 Friedmann and Roblin published a paper "Gene therapy for human genetic disease?" where they mentioned that good DNA can be used to replace the defective DNA in patients having genetic defects. But gene therapy was first applied in treating a four year old girl suffering from an Immune System deficiency in the year 1990. Since then it has been found successful in treating several genetic disorders including SCID , thalassaemia, cystic fibrosis, muscular dystrophy and certain kinds of some cancers.

As with any emerging science, gene therapy it has its own drawbacks like causing side effects and sometimes resulting in temporary cure only.

However Gene therapy is a very promising discipline of life-sciences which is still expanding and scientists are exploring its potential in treating several diseases.

About Author / Additional Info:
A lecturer holding pre-doctoral(M.Phil) degreein Microbiology and Biotechnology.