Human population, all over the world suffers from numerous diseases. Some of these diseases are caused by living organisms, known as pathogenic organisms such as protozoa, fungi, bacteria, viruses, flat worms and nematodes.

Effective and successful therapy (treatment) is available for most, if not all, such diseases. A score of others are caused due to wrong polypeptides (proteins). A polypeptide has a definite amino acid sequence and this sequence confers a specific property to the polypeptide the property of the polypeptide changes, when its amino acid sequence changes.

The amino acid sequence of a polypeptide is specified by the nucleotide sequence of a gene. This phenomenon has been termed as gene expression.

The amino acid sequence and the corresponding nucleotide sequence are said to be collinear. If one or a few nucleotides of a gene are deleted, substituted, or duplicated, the nucleotide sequence of the gene changes and the pew sequence specify a polypeptide of a different amino acid sequence.


This phenomenon is known as mutation and the changed gene as the mutant gene. This polypeptide will have a different property and cannot carry out the function; a normal polypeptide is assigned with. Many polypeptides act as catalysts or enzymes in biochemical pathways, which end in specific products that control body functions of an organism. If one such enzyme’s encoding gene changes in its sequence of nucleotides, a different polypeptide is synthesized: This cannot act as the concerned enzyme.

Consequently, the biochemical pathway ceases and the final product is not formed. This deficiency amounts to a serious malfunction in the body, manifested by several disorders. These disorders are known as genetic disorders. The metabolic disorders of phenylalanine catabolism explain this phenomenon.

Most of the genetic disorders lead to premature death, early or delayed. No effective treatment has yet been discovered for such disorders. However, with the establishment of genetic engineering as a discipline, a small breakthrough has been made in the search for the treatment and cure of these disorders. Attempts have been made to rectify the defective genes, such that the correct polypeptides are synthesized.

This process is known as gene therapy or more appropriately gene replacement therapy. This may be defined as “treatment of a genetic disorder by replacing a defective gene with a normal gene in the cells of an affected tissue of a person in order to restore the normal cellular functions”. It has been considered by many as the most controversial area of genetic engineering. Two types of gene therapies have been recognized: (1) germ cell gene therapy and (2) somatic cell gene therapy.


Germ Cell Gene Therapy

It refers to the replacement of a defective gene with a normal gene in the gametes. The genetic changes conferred to the gametes are passed on to the next generation and perpetuate through generations. Consequently, the gene pool of the population changes with time. Bio-ethics forbids the practice of germ cell gene therapy in all countries of the world.

Somatic Cell Gene Therapy

In this therapy, an abnormal gene in the affected somatic cells is replaced with a normal one, (also referred to as the remedial gene), such that the normal cellular functions are restored.


This change is confined to only one generation i.e. to the individual undergoing the therapy. This genotypic change is not passed on to the next generation. The main thrust is aimed at correcting single gene defects, which follow simple Mendelian inheritance.

Somatic cell gene therapy for complex genetic disorders like Parkinson’s disease has not made considerable headway, since these involve many interacting genes. With the completion of the mapping and sequencing of the human genes, the positions and sequences of the defective genes are known.

This knowledge is used in substituting a defective gene with a normal gene. The size of DNA fragments that can be transferred is limited. In most cases, the transferred gene is not a conventional gene. Instead, a DNA sequence containing the complete coding sequence is engineered and then the sequence is flanked by appropriate regulatory sequences for a relatively high level of expression.

Such relatively short sequences are known as indigenes. Following the transfer, the gene may integrate into the host cell genome or remain as an extra chromosomal element known as epitomes.


A case of somatic cell gene therapy trial will suffice its tremendous promise and potential in curing gene defects in human in the future. W. French Anderson, Michael Blease and Kenneth Culver carried out the first ever gene therapy trial on a four year girl, Asanthi DeSilva at the National Institute of Health (NIH) in 1990. She was suffering from an inherited immunodeficiency disease known as Severe Combined Immunodeficiency Disease (SCID) caused due to a defective adenosine deaminase (ADA) gene.

It leads to the absence of the enzyme, adenosine deaminase. This leads to an impaired functioning of the immune system and death is inevitable within 2 years. The.same was the story with David, born with SCID in Texas in 1971. He had to live in a sterile plastic bubble until his death in 1984.

The sterile plastic bubble gives the- episode the name “David-the bubble boy”. Coming back to Asanthi episode, her affected bone marrow stem cells were transformed in vitriol by correct ADA gene and then re-implanted into the bone marrow. (Note: Stem cells are undifferentiated pluripotent cells possessing the potential to develop into any one of the several different kinds of cells.). Four months later, a second patient, Cynthia Cutshall, another SCID patient, was treated by the same protocol.

After the following three years, 50% and \% of the circulating T-lymphocytes of Asanthi and Cynthia were found to contain the correct ADA gene, respectively.


This demonstrated that the effectiveness of the therapy varies from person to person. SCID and other defective enzymes associated with the nucleic acid metabolism are outlined in.