Patients and Carers

What is gene therapy?

Gene therapy is a type of medical procedure that could treat or prevent disease by replacing or modifying the DNA in a person’s cells. Many human diseases are caused by a defect (called a mutation) in either a single gene or set of genes. Gene therapy allows 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 the text in 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 built incorrectly it causes a disease because the protein is faulty or missing, gene therapy may be able to restore the ability for the patients own cells to create normal and functioning protein and undo the disease. However, researchers have to solve numerous challenges before gene therapy becomes common, 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 and then into the target cell, 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.

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 organs 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.

a. Viral vectors

Researchers can take viruses we are exposed to every day 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 inserted into the cells nucleus and corrects or replaces the defective 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 SYNTHETIC vectors

Although non-viral vectors do not have viruses’ natural evolved infective ability to penetrate cells, we believe they represent the long-term future of gene therapy.

Knowledge about viruses and cell biology, combined with ever-evolving engineered synthetic 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 healthy 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 topically applied to the skin.

Pre-clinical data has shown significant levels of collagen VII in skin after AP103 is applied topically. Although the corrected DNA does not permanently become part of the patient’s cells so 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.