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What is gene therapy?

Gene therapy is a therapeutic technique in which changes in genes are made to treat various health conditions. Depending on the need, a gene can either be replaced, removed or added into the genome of an individual. 

Genes are stretches of DNA that code for everything in your body. They make proteins for building body structures and enzymes for carrying out various functions in the body. Your genes also determine your physical structures ranging from your voice tone, your hair colour and the colour of your eyes. 

Human genome (all of its DNA) has about 20,000 to 25,000 genes. Every cell in the human body has one copy of the complete genome. Genes are present in pairs—every gene has two copies one from each parent. Alleles are the two forms of the same gene with slight variations in their DNA sequence. It is the differences in these alleles that give everyone unique features.  

However, a majority of the DNA is made of non-coding genes. Only 1% of our total DNA has genes coding for and producing proteins.

Malfunctions or mutation in certain genes manifests in the form of disorders or diseases. Mutations refer to unwanted changes in the DNA that affects the function of the gene.

  1. Types of gene therapy
  2. Gene therapy procedure
  3. Types of viral vectors used for gene therapy
  4. Gene editing
  5. Gene therapy uses
  6. Possible issues with using gene therapy

Depending on which cells in the body it is performed on, there are two types of gene therapy:

Somatic gene therapy

This type of gene therapy is done to correct problems in somatic cells (all cells of the body apart from sperms and eggs and the cells that produce them). So, this method is used to treat problems in only one person (not his/her offsprings). 

Right now, it is not possible to make changes in all the body cells. So, somatic gene therapy is done to correct problems in genes that are only present in specific tissues. For example, introducing a new gene in the bone marrow of the person to correct disorders of the blood. Even then, not all cells of the tissue may become transgenic (have the new gene) but changing the gene in only a few cells may correct the disease. 

Germline gene therapy

In germline gene therapy, genes are introduced into the germline cells—sperms, ova or the developing embryo. However, experts suggest that there is no knowing where a gene might end up when introduced into the genome and what mutations it may lead to. Also, there are ethical issues in doing this therapy. So far, germline gene therapy has not been performed anywhere.

Gene therapy is most commonly done using viral or plasmid (bacterial cloning) vectors.

Viral vectors (carriers) are basically modified versions of normal viruses that cannot cause disease, as the disease-causing nucleic acid (DNA/RNA) sequence of the virus is replaced in a lab with the gene that needs to be added to the human genome. Along with the gene, various other parts of the nucleic acid that control the expression of the gene (make sure that the gene works) are also added in the vector.

Plasmid, on the other hand, is circle DNA that does not have a protective coat but can be artificially put in a lipid or synthetic membrane to introduce into healthy cells. 

Some important points to consider before choosing a viral vector include:

  • The size of the gene that needs to be inserted
  • The target cell: whether it keeps on dividing or not. 
  • The target location of the gene. If a gene gets inserted into the wrong location, it might lead to various problems—even cancer. So it’s important to determine the precise location for insertion of a gene.
  • How will the vector work: by inserting a gene inside the genome of the person or by staying as an independent entity in the cell? If the gene is inserted into the genome of the cell, it would be passed onto the next generation of cells.
  • Presence of antibodies in the person against the vector. If an individual already has antibodies against a virus in their blood, then these antibodies would recognise the virus as a threat and neutralise it or destroy the cell that contains the vector virus.

Once everything is selected, gene therapy can be done in one of the following ways:

In vivo gene therapy

For this therapy, the gene is directly injected into a person’s body. The vector can be injected directly into a target tissue or intravenously or intramuscularly. In case of gene therapy for cancer or a tumour, the injection can be given in the tumour itself.

Ex vivo gene therapy

For this therapy, specific cells from a person’s body are taken out, modified inside a lab and then replanted. In ex vivo therapy, it is preferred that the new gene gets integrated into the genome of the cell so it can be transferred to new cells when the original cell divides and gives long-term clinical effects. 

Cells from allogenic sources (from a donor, for instance) can also be used for this therapy. These have comparatively fewer supply and manufacturing issues. 

However, autologous sources are generally prefered since they don’t evoke an immune response. (Autologous means cells and tissues taken from the patient's own body.)

The following are some types of viral vectors that are used for gene therapy:

  • Adenovirus vectors, especially those derived from the serotype 5 (Ad5 vectors):These vectors are more commonly used for short-term therapy. They don’t get integrated into the genome of the person, and as a result, get lost over the course of time. Adenovirus vectors also stimulate a strong immune response in the body, which is considered to be a disadvantage in a gene therapy vector. However, they may be used for short-term uses like reducing inflammation, and destroying cancer or tumour cells and can be integrated into both dividing and non-dividing cells in the body.
    The human body has various kinds of cells which can either be dividing or non-dividing. Non-dividing cells are those that have differentiated into specialised tissues. A majority of the cells in an adult human body are non-dividing. These include skin cells, neurons (brain cells), and adipocytes (fat cells). However, certain cells in the brain, skin and blood are constantly dividing.
  • Murine leukaemia virus (MLV) vector: MLV is a retrovirus—an RNA virus that uses an enzyme called reverse transcriptase to make a DNA copy of its genetic material. This DNA then gets integrated into the genome of the host cell. MLV vectors utilise this property of the virus to add new genes into the DNA of a person.
    On the plus side, the gene can be sustained in the body for a long time. On the downside, these vectors can only be added to dividing cells, severely reducing their target range. Another problem with MLV vectors is that they have a risk of mutations if they get integrated into the wrong place.
  • Lentivirus vectors: Lentiviruses are a type of retroviruses just like the MLV vector that have recently gained more attention from the scientific community for their potential benefits. The speciality of these vectors is that they can infect non-dividing cells, too. In particular, the AIDS virus—Human Immunodeficiency Virus—is being used for repair of neurons. More studies are underway to develop an HIV-based gene delivery system for diseases like cystic fibrosis, cancer, viral infections, haemophilia, retinitis pigmentosa and more. The greatest concern with an HIV-based vector is that the virus may replicate during the making of the vector and the person may end up getting HIV infection along with getting the new gene.
    To avoid this, HIV vectors without the genes that are necessary for them to cause infection are being produced now.

Gene editing is a bit different from standard gene therapy. In this procedure, instead of inserting a gene, the machinery for gene editing is inserted into the host cells. This machinery mainly includes:

  • Nucleases: Enzymes that break pieces of DNA at specific locations. 
  • Gene templates: stretches of DNA sequences that ensure that the new DNA made (in place of the broken pieces) is the correct sequence. 

So, the editing machinery not only helps add a new gene but also inactivate, delete or edit/correct the defective gene. 

The machinery can be introduced into host cells by either in vivo method or ex vivo method. Some gene-editing tools include:

  • Crisper/Cas9: Clustered regularly interspaced short palindromic repeats–associated nuclease Cas9
  • ZFN: Zinc finger nuclease 
  • TALEN: Transcription activator-like effector nuclease 

Crisper/Cas9 is more suited to ex-vivo therapy. It is much easier and cost-friendly to develop than the other two tools and is hence been more widely used.

Gene therapy has a wide range of applications but is especially suited to long-term delivery of a new gene to a person who has a mutation or a flaw in a single gene. The first-ever gene therapy was given to a girl named Ashanthi DeSilva in 1990. The girl had a rare genetic disease called severe combined immunodeficiency syndrome (SCID). She lacked an enzyme called adenosine deaminase (ADA). SCID severely weakens the immune system and makes the person prone to infections. (Read more: Adenosine deaminase test)

The girl was given the ADA gene through a vector and she showed the presence of the gene product even 12 years after the therapy. 

In 2003, China became the first country to approve a gene therapy: it was for head and neck cancer. After that, many more therapies have been approved all over the world, mostly for various kinds of cancer. More therapies are under trial for the treatment of rare genetic disorders, autoimmune diseases and wound healing.

The following are some issues that may hinder the proper implementation of gene therapy for the masses:

  • Fast-track decision making: Some gene therapies are supported by regulators for fast-track approval. Experts suggest that this may cause new therapies to be introduced into the market after only the preliminary trials and lack of safety information. 
  • High cost: Gene therapies that are currently being used are really expensive. If this remains the trend, chances are it may remain out of reach for many people. Even though the prices are expected to fall once more therapies are available for common health conditions, the cost of therapy for severe conditions may still be high. According to one 2018 estimate, published in CADTH Issues in Emerging Health Technologies, the budget impact of Alzheimer’s gene therapy could be as high as £72 billion (₹6,66,070 crore). (CADTH is the Canadian Agency for Drugs and Technologies in Health).
  • Staff and facilities: Gene therapy is a really specialised treatment. Hence, it needs highly skilled staff who are able to maintain all the US FDA (Food and Drug Administration), EMA (Europen Medicines Agency) and national medical body regulations to ensure vector purity and sterility and consistency of the treatment. So, it may only be available at limited places.
    Also, the government will have to increase early screening of all those diseases that will hence become treatable with gene therapy since early treatment minimises damage and disability.


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  3. OpenLearn [internet]. The Open Univeristy. UK; Gene therapy
  4. Iyama Teruaki, Wilson David M., III. DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst). 2013 Aug; 12(8): 620–636. PMID: 23684800.
  5. Cancer Research UK [Internet]. London. UK; How cells and tissues grow
  6. Department of Biology: Kenyon College [Internet]. Kenyon College. Ohio. US; What is gene therapy?
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