The gene therapy is an artificial genetic technique used in order to cure any genetic defect by replacing a defective gene with a normal one using harmless vectors.

In a simple language, we say that gene therapy is a technique used to prevent or cure any genetic disease or some.

A defective gene can cause “ailment.”

(Ailment: combinedly used for  disorder, illness, sickness or disease).

The cell is a basic building unit of any living entity and carries DNA in it.

The DNA is an “information storage unit” that inherent genetic information from one generation to another generation.

By transcribing the intermediate mRNA from the DNA, it produces a macromolecule needed for performing any kind of function for cell, called a protein.

That is why it is very important that the DNA remains unchanged generation after generation.

If any change or mutation occurred in the DNA, especially in the coding regions of it (called a gene), it causes abnormality or abnormal phenotype.

Some of the common types of mutations are deletion or addition of some sequences, loss of gene expression and single nucleotide polymorphism.

In a single nucleotide polymorphism, insertion or deletion of a single nucleotide causes genetic defects.

However, the effect of mutation varies from cell to cell.

If the mutation occurred in the DNA of somatic cells, it can affect some of the body tissue which is made of that type of cells.

If the mutation occurred in the DNA of germ line cells, it affects the whole organism originated from those cells. Even that mutation can spread to the next generation of it.

The genetic defect may not be curable. So it is necessary to replace that mutant gene with a healthy gene.

The concept of gene therapy or gene transfer is originated due to this reason.

Before understanding how gene therapy works, we have to understand what actually a gene therapy is.

We are starting a new series of articles on gene therapy. This article is just an introductory basic article which clears your fundamentals regarding gene therapy and how it works.

What is gene therapy?

A defected gene is replaced by introducing a new healthy gene using some of the artificial methods is known as gene therapy.

However, it is very necessary that what method we are using for gene therapy should not be harmful to the patient.

The overall idea of gene therapy is given into the figure below,

How does gene therapy work?

The GOI, gene of interest inserted into a vector. The vector transfer the GOI in the target cell, insert it into the target site.

Now, the gene sequence is incorporated in place of a faulty or mutant gene.

The gene therapy is used,

  • To replace a fully mutant gene
  • To introduce a new gene or DNA sequences that are missing
  • To inactivate mutant gene (Gene knock out)
  • To insert a totally new gene

These are some of the common aims of any gene therapy experiment, using a definite vector these aims can be achieved.

The “vector” used here is not a plasmid vector, it is a vehicle used for gene therapy.

The gene therapy is of two main types: in vivo gene therapy and ex vivo gene therapy.

“In ex vivo gene therapy, the whole experiment of gene transfer performed inside the lab (outside the body).”

“In the in vivo gene therapy, the gene is directly inserted inside the body.”

The in vivo and ex vivo gene therapy

We will give you a detailed explanation of each gene therapy in our upcoming article.

If the gene of interest inserted into the somatic cells, it is called somatic gene therapy and if it is done on germ cells, it is known as germline gene therapy.

Read some interesting articles:

  1. Transposons: A Jumping Entity and a Foe with Benefits
  2. Chromosome 6p deletion: A reason for no pain, no hunger and no sleep

How does gene therapy work?

There are three main components of gene therapy,

  1. Gene of interest
  2. A vehicle or vector
  3. Target site or target cell

The main three component of gene therapy

The gene of interest is the new normal or healthy gene that we wish to introduce in place of the mutant gene.

The gene of interest often denoted as “GOI”, is carried by the vehicle or a vector. In the first step, the GOI introduced in the vector.

Several vectors such as viruses, transposons or other naked DNA are often used as a carrier of genetic material.

If the virus is a vector, before doing the gene transfer, the virus is modified in such a way that it can not infect the cell in any way.

Retroviruses, adenovirus and adeno-associated viruses are frequently used as a vehicle for gene therapy.

In the next step,

The vector introduced a new gene to the faulty infected cell or at a target site.

The target site is a location where our GOI going to insert.

The vector is inserted into the target cells using some of the artificial methods, intravenous injection is one of those methods.

After infection, the vector inserts a new gene at a specific location, the naked vector is engulfed and destroyed by the host cell.

Now, the new gene replicated into the host genome produced new copies of it. Ultimately the affected cells are replaced by the new cells (having the new gene).

The gene of interest now transcribed into new mRNA and translates new healthy protein.

Broadly the mechanism of how gene therapy works is shown into the figure below,

See the figure,

The mechanism of gene therapy

The gene therapy approach is more promising for somatic tissues in which a certain part of the body contains the mutant gene.

For example, for the Parkinson disease in which specific part of the brain is non-function, scientists are trying gene therapy for that. However, it is under trial phase.

Another example of ex vivo gene therapy is the sickle cell disorder,

The abnormal cells are collected from the blood or bone marrow. The gene of interest is inserted with the help of some physical or chemical agents inside the cell.

Gene Therapy

A gene therapy book from Springer.

The altered cells are grown in the lab and inserted back in the bone marrow or blood stream.

The repaired cells grew faster through the cell division and replaced the older abnormal cells.

The germline gene therapy is trickly prohibited by FDA because of the higher risk factors associated with it.

And by the way, “playing with an embryo or altering embryo is ethically against nature.”

Though gene therapy is a promising method, the success rate of gene therapy is fewer.

Additionally, the risk associated with any type of gene therapy is unknown, we do not have any idea about what harmful effect it can cause.

The patient may die or he or she may suffer from some other type of infection or cancer.

Nonetheless, new approaches to gene therapy such as the use of transposon and CRISPR-CAS9 is more promising and safer.

“The sleeping beauty transposon system”, futuristic gene therapy uses a transposon to introduce a new gene at a specific location.

Read our article on the SB transposon system it contains all information and mechanism on how it is done: Sleeping Beauty Transposon System: The Future of Gene Therapy

Another method is CIRPSR-CAS9 a bacterial system used for gene editing.

Both methods are immensely target-specific having a huge success rate. However, it required some time and extensive trial/testing to gain attention in mainstream clinical uses.

Likewise the viral vectors some of the artificial nonviral vectors are:

  • Liposome or lipoplex
  • Naked DNA
  • Nanoparticles
  • The process of nucleofection

Thanks to the nanotechnology, some of the nano molecules such as liposome and lipoplex are now available that effectively facilitate gene transfer without using any virus.

We will talk about all type of vectors in our next meaty-pillar post. The classification of gene therapy is given below,

Viral and non-viral vectors for gene therapy

Additionally, monogenic disorders treated well by using gene therapy. The monogenic disorders are occurred due to the involvement of only a single gene.

However, many mutations can occur in a single gene.

In contrast to this, more than one genes are involved in the multigenic disorders that are hard to treat with gene therapy.

Due to the involvement of many genes, it is challenging to replace them.

Besides this, gene therapy has several other limitations that make it unrealistic in recent time.

  • The effect of gene therapy is not linear, it may work sometime or sometime not.
  • The use of a virus as a vector can induce an adverse immune response.
  • It is possible that it may miss the target sometime and disrupt other genes’ function.
  • It can affect some healthy cells too.
  • The oncogenic activity can be stimulated using virus-mediated gene therapy.

Read more:

  1. DNA fingerprinting
  2. DNA Replication class 1: General process of DNA replication

Recent trends in gene therapy:

  • 2017 was one of the biggest milestones for gene therapy research in which the FDA approved gene therapy for the first time.

It was for the sickle cell anaemia, a monogenic blood disorder.

  • Due to the harmful nature of adenovirus, the scientists are now using AAV for gene therapy.

Also, it is now proven that the AAV can transfer the gene to both dividing as well as non-dividing cells

It used in the retinal as well as cancer gene therapy.

Additionally, ongoing trials on animal model confirm that AVV gene therapy is one of the hopeful approaches for curing cancer.

  • Gene therapy for cystic fibrosis, Duchenne muscular dystrophy, Haemophilia (A and B), Thalassemia, Severe combined immunodeficiency syndrome and cancer are doing well on animal models.

Hopefully, these gene therapies might available until 2020 for routine medical use.

Apart from all these, the discovery of CRISP-CAS9 and SB transposon system and their recent advancement clearly indicates that the future of gene therapy is secure.

Conclusively we can say that gene therapy is not ready for the present medical scenario, but it might fully accessible in future for mankind.

Any gene therapy going to main clinical trial phase must be safer, effective and target specific. 

If you want more information and protocol on gene therapy, you can purchase these Springer books:

Gene Therapy Gene Therapy

Some of the approved gene therapy:

FDA recently approved gene therapy for some disorders are enlisted below,

1. Name: onasemnogene abeparvovec-xioi

Manufacturer: AveXis, Inc

Gene therapy for the spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene for the treatment of pediatric patients of less than 2 years old.

For Licence information click here.

2. Name: Autologous Cellular Immunotherapy

Manufacturer: Dendreon Corporation

Gene therapy for prostate cancer, treatment of asymptomatic or minimally symptomatic metastatic castrate resistant.

For Licence and other information click here.

3. Name: voretigene neparvovec-rzyl

Manufacturer: Spark Therapeutics, Inc.

Gene therapy for the retinal dystrophy (biallelic RPE65 mutation). This is an AAV based gene therapy therefore viable retinal cells must be present for therapy.

For Licence and other information click here.


Germline gene therapy is not yet “completely” approved from the FDA and USA government for commercial mainstream use due to the lower success rate and risk associated with it.

Still, some of the partially approved (non- germline) gene therapies are listed above.

The recent gene therapy progress on sickle cell, congenital amaurosis (blindness) and the bleeding disorder is giving hope for their use in the upcoming years.