Gene Therapy


The genes in your body’s cells play an important role in your health indeed, a defective gene or genes can make you sick.

Recognising this, scientists have been working for decades on ways to modify genes or replace faulty genes with healthy ones to treat, cure or prevent a disease or medical condition.

Now this research on gene therapy is finally paying off. Since August 2017, the U.S. Food and Drug Administration has approved three gene therapy products, the first of their kind.

Two of them re-program a patient’s own cells to attack a deadly cancer, and the most recent approved product targets a disease caused by mutations in a specific gene.

Gene therapy can be performed both inside and outside the body.ion


Sometimes the whole or part of a gene is defective or missing from birth, or a gene can change or mutate during adult life. Any of these variations can disrupt how proteins are made, which can contribute to health problems or diseases.

In gene therapy, scientists can do one of several things depending on the problem that is present:

They can replace a gene that causes a medical problem with one that doesn’t add genes to help the body to fight or treat disease or turn off genes that are causing problems in order to insert new genes directly into cells, scientists use a vehicle called a “vector” which is genetically engineered to deliver the gene.

Viruses, for example, have a natural ability to deliver genetic material into cells, and therefore, can be used as vectors. Before, a virus can be used to carry therapeutic genes into human cells. However, it is modified to remove its ability to cause an infectious disease.

Gene therapy can be used to modify cells inside or outside the body. When it’s done inside the body, a doctor will inject the vector carrying
the gene directly into the part of the body that has defective cells.

In gene therapy that is used to modify cells outside of the body, blood, bone marrow, or another tissue can be taken from a patient, and specific types of cells can be separated out in the lab. The vector containing the desired gene is introduced into these cells. The cells are left to multiply in the laboratory, and are then injected back into the patient, where they continue to multiply and eventually produce the desired effect.


Cells are the basic building blocks of all living things; the human body is composed of trillions of them. Within our cells there are thousands of genes that provide the information for the production of specific proteins and enzymes that make muscles, bones, and blood, which in turn support most of our body’s functions, such as digestion, making energy, and growing.

How our gene therapy works:
Gene therapy offers the ability to permanently correct a disease at its most basic level, the genome. And could offer cures for many conditions that are considered incurable at this time. It is a flexible treatment option and gene therapy has the potential to treat a variety of illnesses by:

Replacing missing or defective genes which can cause inherited or acquired disorders. Delivering genes that add needed proteins to the body. Delivering genes that enhance the body to resist disease and perform at higher levels. Introducing genes which stimulate cell growth and heal damaged tissue. Gene therapy offers patient alternatives to regular daily maintenance. Patients suffering from life-threatening disease are often forced to endure swallowing pills or daily/weekly injections to treat and/or monitor their disease. Gene therapy could ease the burden of enduring the disease by offering the promise of 1-2 treatment injections in a patient’s lifetime with no need for long-term follow-up. 

With the remarkable progress in genetics, we believe gene therapy will prove to play an increasingly prominent and transformative role in medicine. Gene therapy has the potential to treat and maybe cure monogenic diseases. Most monogenic diseases are ones for which a protein is defective or not being expressed. As such, gene therapy has the potential to address many of these congenital disorders. There is also a broad opportunity to apply gene therapy for acquired diseases as diverse as HIV, heart failure, Alzheimer’s and more.


Gene therapy has come a long way from its 20th century conceptual origins. Here are some key moments in the history of the technology.


Gene therapy today is a newly confident field, buoyed by a number of recent successes and significant technological strides. We now understand far more about the human body’s reaction to viral vectors, which are used to transfer genetic material into your cells. Past tragedies are now understood to be caused by either:

Virus Type
Virus types that are inherently immunogenic are ones where the body reacts in an aggressive manner in response to injection. Certain adenoviruses are known to be dangerous immunogenics in some cases. Particularly when the dosage used is too high. The robustly studied Adeno-associated Virus (AAV) is BioViva’s vector of choice. This has an excellent safety profile in both research studies and trials and is one of the most popular vectors in the gene therapy field today.

Dosage is extremely important when considering both safety and efficacy in gene therapy. Two decades of advancement have revealed which dosage window is safe and effective when using different types of viral vectors. By limiting exposure, these risks are diminishe greatly. 

Initial research was focused on viral vectors that integrate their DNA sequence into the human genome. This means that any delivery is permanent, and the target gene will be incorporated into the patient’s genome – meaning it will also be passed on when that cell divides. This sounds like a good idea on paper, but the reality is that initially researchers had little knowledge regarding where this DNA would integrate. We have made progress on this, but it is still extremely challenging to pick and choose a safe region of the genome to integrate your chosen gene sequence in. The problem with many viruses is that they have a tendency to integrate DNA in specific regions which may be detrimental to interfere with. In the case of those patients with severe immunodeficiency, in which 3 sadly developed leukemia, this is now understood to have been caused by something called insertional mutagenesis. Insertional mutagenesis occurs when an integration happens next to something called an oncogene. An oncogene is a gene with the potential to cause cancer if it is altered or expressed differently. Insertion of a DNA sequence within or beside an oncogene may affect expression, and therefore lead to cancer in a minority of patients. 

How do we resolve this?
The vast majority of gene therapy today uses non-integrating vectors, not integrating ones. Perhaps the two most popular of these are adeno associated viruses or lentiviruses which have been engineered to inject DNA as something called an episome. An episome is a small circular strand of DNA which contains the therapeutic gene sequence inside this sequence will be translated by the cell into a new protein, but i  remains outside of the host genome. This means it won’t be replicated when the cell divides, so expression is semi-permanent in the majority of dividing cells. In slow dividing cells however, expression will continue for a long
period of time.


As of Spring 2017, according to US NIH data:

71 gene therapy trials have, will, or are taking place currently using adeno-associated viruses. 459 gene therapy studies are now closed. 179 gene therapy trials are currently open or will be recruiting in the near future 5062 studies in total have taken place, are taking place, will take place, or have been terminated.

The first product to be approved was Gendicine in 2003, for the treatment of head and neck squamous cell carcinoma.

This was followed by Oncorine (H101) for late stage refractory nasopharyngeal cancer in November 2005.

The first gene therapy product to be approved in 2012 by the EMA was UniQure’s Glybera (alipogene tiparvovec) for lipoprotein lipase deficiency. Strimvelis, manufactured by GlaxoSmithKline, was approved in 2016 for ADA-SCID. Zalmoxis (allogeneic T-cells altered through ex vivo gene therapy), an immunogene therapy for hematological malignancies was given conditional approval in 2016.


Imylgic (talimogene laherparepvec), an oncolytic gene therapy was approved by the EMA and FDA in 2016 and 2015.

Neovasculagen was approved by the Russian Ministry of Health Care in 2011 for the treatment of atherosclerotic Peripheral Arterial Disease (PAD) and Critical Limb Ischemia (CLI), after passing a phase I/IIa trial. The therapy delivers a copy of the Vascular Endothelial Growth Factor (VEGF) gene.


Approval can be a slow process, but many studies have indicated positive results in a range of chronic and debilitating conditions. We summarize some of the successes seen so far, pending further study:

Immune Deficiencies

DiseaseBoth ADA-SCID and SCID have been successfully treated using gene therapy and were some of the first diseases to be targeted. New viral vector design addresses the risk of leukemia that was found in a minority of some patients in the early trial (Blaese et al,. 1995), although a majority were effectively cured. The most recent trial at UCLA was highly successful, with 9 of 10 patients treated able to live a normal life outside of a sterile environment.

Parkinson’s Disease

Parkinson’s disease is characterised by a loss of dopamine neurons in the substantia nigra region of the brain.

A therapy called ProSavin has been tested in the UK and France. It works by delivering the genes required for dopamine production to new cells, designed to replace those dopamine cells which have been lost. Patients have shown significant movement improvements and it has an excellent safety profile (Palfi et al,. 2014).


Hemophilia causes a deficiency in clotting enzymes, which causes internal bleeding and fatal bleeding in response to minor injury. Research using adeno-associated viral vector delivery of the factor IX protein has shown some efficacy in trials so far, with patients demonstrating increased expression of the protein (Nathwani et al,. 2014).


Beta-Thalassemia caused a defect in red blood cells ability to carry oxygen through the blood. Affected individuals require regular transfusions to survive. A small trial in 2007 in which a patient’s blood stem cells underwent ex-vivo gene therapy outside the body before re-transplantation, was able to induce correct beta-globin expression even 7 years after the therapy (Nienhuis,. 2013).

Leber’s Congenital Amaurosis

Leber’s congenital amaurosis is a rare inherited retinal degenerative disorder which leads to progressive loss of vision and eventually blindness. It is frequently caused by a mutation in the RPE65 gene and a gene therapy approach providing an additional functional copy of this gene, using an AAV vector again, has proved able to restore vision without side effects (Maguire et al. 2008).


As cancer is more of an umbrella term for a whole range of diseases, there is a whole host of research using gene therapy technology to fight cancer – from immunotherapy CAR-T cells, edited to better track and hunt down cancer cells to specific viruses designed to eliminate cancerous cells. Already approved Imylgic and Zalmoxis, mentioned above, are good examples of this.

Cystic Fibrosis

While the build up of accumulated cellular debris in patients lungs makes cystic fibrosis a challenging disease to tackle, researchers are working on a cure. A nebulised gene for the CFTR delivered into patients lungs has been proven to stabilise lung function to a degree with no negative effects reported (Alton et al., 2015).

These are simply a few of many, many more ongoing trials. There is undeniably still work to be done in many diseases, but efficacy is building and the safety profile of gene therapy strategies today is excellent. The budding success of this approach in so many conditions, especially with regards to inherited monogenic conditions, is extremely encouraging for the field as we look ahead.