Patients and Carers

What is gene therapy?

Gene therapy is a type of medical procedure that could treat or prevent disease by modifying the DNA in a person’s cells. Many human diseases are caused by a defect in either a single gene or set of genes called a mutation. Gene therapy could allow doctors to switch off a non-working or faulty or missing gene, replacing it with a healthy copy or introduce a new gene into the body altogether.

Similar to an instruction manual, genes are responsible for telling cells how to build a specific protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to restore the ability for the cells of the body to create normal and functioning copies of the protein. However, researchers have to solve numerous challenges before gene therapy will become the preferred approach to treating disease, including better ways to deliver corrected genes and manage the body’s response to their delivery.

How does gene therapy work?

Inserting a new gene directly into the body, as naked DNA, usually does not work. That is why researchers need to use a delivery system, also called a vector. The vector carries the healthy gene (known as therapeutic gene or transgene) to the target cells, tissues or organs.

Choosing the right vector is critical as it effects how the patient has the gene therapy applied to them, how often the therapy needs to be applied and an easy-to-use efficient vector will allow researchers to potentially expand the use of a gene therapy within diagnostics, biotechnology, and basic science research.

There are two ways of delivering a vector: it can either be transferred directly into cells while they are still in the patient (in vivo); or a sample of the target cells is taken from the patient, exposed to the vector in the laboratory, and then returned into the patient (ex vivo).

Broadly speaking there two types of vectors; viral and non-viral (or ‘engineered’.)

a. Viral vectors

Researchers can take every day viruses but modify them so that when they are used to ‘infect’ cells with the new genes, this can happen without making the person ill. Once administered into the body, the virus’ genetic material, which now includes the healthy gene, is integrated into the cell DNA and corrects the defective or mutated gene.
Despite the viruses being specifically ‘programmed’ to become vectors, the body’s immune response remains one of the main hurdles to this approach, as it tries to tackle the virus.

B. Non-viral or engineered vectors

Although non-viral vectors do not have viruses’ natural infective ability to penetrate cells, they represent the long-term future of gene therapy.
Knowledge about viruses and cell biology, combined with ever-evolving high-tech biomaterials are helping researchers create synthetic or man-made vectors that are able to deliver healthy genes in more a stable manner, without stimulating the immune system or destroying living cells. Additionally, they are relatively low cost and easy to produce.

What is the role of gene therapy in epidermolysis bullosa (EB)?

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a particularly severe form of EB and it is caused by mutations in a single gene, COL7A1, which codes for type VII collagen, i.e. it is responsible for instructing cells on how to produce the ‘velcro’ that keeps the first two layers of the skin together, the epidermis and the dermis.

Production of this “normal” fully functioning collagen by skin cells could potentially be returned to people with RDEB thereby restoring the elastic structural integrity of the skin. In doing so, skin will be much less fragile and much more resistant to damage and blistering.  In turn, the quality of life for patients with RDEB could dramatically improve.

What is AP103 and how does it work?

AP103 is a new platform for gene therapy that involves a synthetic vector called a polymer. This specific polymer’s full name is HPAE, Highly Branched Poly (β-Amino Ester), and it is designed to deliver a healthy collagen VII gene into skin cells. It is also topically applied to the skin.

Pre-clinical data has shown significant levels of collagen VII in the skin after AP103 being applied topically. Although this means that the corrected DNA does not become part of the patient’s DNA and that AP103 has to be re-applied, it also makes it less likely to provoke an immune response in the body and reduces the risk that the new DNA will cause cancer-causing mutations in the patient’s genes.

The way AP103 works is different to other gene therapies in development in EB which either use viral vectors or where skin cells are taken from the patient with EB, modified with gene therapy and transplanted back onto the wounds to heal them.

Page last updated: 04 May 2018