Gene Therapy

Gene therapy, conceptual image

What is Gene Therapy?

Gene therapy is an experimental technique used in treatment of malfunctioning genes, whereby a deficient or defective gene is replaced by a working gene, so that the body can make the proper enzyme or protein and as a result eliminate the origin of the disease.
Gene therapy is therefore targeted to “genetic metabolic diseases” in which a faulty gene causes an enzyme to be either absent or ineffective in catalyzing a particular metabolic reaction effectively.

There are a number of approaches for correcting defective genes:

The most common approach is inserting a gene into a non-specific location within the genome, replacing a nonfunctional gene.
Through selective reverse mutation, the malformed gene can be repaired to attain its normal role.
Via homologous recombination, the normal gene is exchanged for the abnormal gene
Alteration of the regulation of a particular gene.

How does Gene Therapy work?

To insert the corrected gene into the patient’s targeted cell, a carrier molecule, called a vector must be used. The most common form of vector is a virus which has been genetically modified to contain human DNA within it. The viruses are modified by replacing the deformed gene with the genes encoding for the desired effect. Thus the virus can be used as a 'vehicle' to carry the good genes into the targeted human cell in a pathogenic manner . The target cells are usually a patient’s liver or lung cells, where the viral vector transfers the therapeutic gene into the target cell. The therapeutic gene generates the production of functional proteins and restores the cell to its normal state 

 

The types of viruses used in gene therapy

There are six main types of viruses used as vectors in gene therapy (shown in table below):


1. Retroviruses - A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells. Human immunodeficiency virus (HIV) is a retrovirus.

2. Adenoviruses - A class of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans. The virus that causes the common cold is an adenovirus. 

3. Adeno-associated viruses - A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19.

4.Herpes simplex viruses - A class of double-stranded DNA viruses that infect a particular cell type, neurons. Herpes simplex virus type 1 is a common human pathogen that causes cold sores.13

5. Alphaviruses- a single stranded positive sense RNA, particularly used to develop viral vectors for  the Ross-River virus, Sindbis virus, Semliki Forest virus and Venezuelan Equine Encephalitis virus.

6. Vaccina or pox viruses- a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome of approximately 190 kb in length, which encodes for around 250 genes. Can accept as much as 25kb of foreign DNA making it especially useful in expressing a large gene in gene therapy.