There are two main delivery methods for gene therapy: ex vivo (outside the body) and in vivo (inside the body).

Ex vivo requires harvesting a patient’s cells and then reintroducing them into the patient. These therapies are often evaluated for blood-related disorders, such as leukemia and lymphoma, as well as some rare diseases.

The second approach to gene therapy, in vivo, is better suited for targeting specific organs in the body. This technique uses a vector, which serves as a delivery vehicle, to shuttle genetic material directly to patients’ cells.

Pfizer is currently focused on developing in-vivo adeno-associated virus (AAV) gene therapies for patients with rare diseases. These patients have inherited genetic conditions that are caused by a single-gene mutation, such as hemophilia, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis (ALS). When the mutation occurs, it causes a defective protein to be produced, leading to the patient’s specific medical condition.

“Our goal is to replace a mutated or defective gene with a healthy or more effective copy,” says Clark Pan, Vice President, Gene Therapy and Discovery Biology. “This would allow the patient to be able to produce a version of the protein, which would help the body to function as expected.”

While many viruses can make people sick, they have another attribute that can help in medicine: They’re very adept at delivering genetic material into cells. And AAVs are ideal vectors for genetic material because they don’t cause illness in humans. Scientists engineer the AAV so it’s transformed from a naturally occurring virus into a protein shell that can deliver copies of therapeutic genes to targeted tissues and organs in the body. “And 96% of the AAV’s genetic information is replaced by the therapeutic gene,” says Pan.

“With current research underway, that’s absolutely not true,” says Ricardos Tabet, Senior Principal Scientist, Rare Disease Research Unit. The amount of genetic information delivered in gene therapy is very small and precise. “We have a very specific gene that will be replaced in a very well-controlled way inside the cell.”

In contrast, to make a “super baby,” it would require altering the entire book of DNA, all the genetic information needed to build and sustain life in that individual.

“With AAV gene therapy,” says Tabet, “we are basically working on one defective line from that book without modifying the entire DNA of that person.”

While gene therapy is not at the cure stage yet, treatments can be transformational and help slow the progression of illness in patients with rare diseases. “It has the potential to change the lives of patients,” says Tabet, whose research is focused on gene therapy for patients with neurodegenerative diseases such as ALS. In ALS patients, who already have some neurodegeneration, a gene therapy can help slow the destruction of neurons and prevent cells from dying, which will reduce or stop some symptoms from occurring. “This can be a very fast-moving disease where patients are in need of treatments,” says Tabet. “We have a window where we can delay the progression of the disease, but it’s not necessarily a cure.”

For patients with conditions such a hemophilia B, a blood clotting disorder, a potential gene therapy could improve their quality of life. Under the traditional standard of care, patients need to visit a clinic multiple times a week to receive therapeutic transfusions. “For patients living with hemophilia, there are examples now where they can build a normal life after a single dose of gene therapy,” says Pan. “That means children can go out to play soccer without having to worry about an uncontrollable bleed, or the constant reminder of their disease by going to the hospital for injections multiple times a week,” says Pan.

Currently, Pfizer and much of the field are focused on developing gene therapies for rare diseases caused by a single-gene mutation. In these conditions, there most often is a clear understanding of how the gene mutation causes the disorder and what healthy gene is needed to correct it.

“We’re going for those areas with high unmet needs—where there is not necessarily an available therapy, but we have a very defined cause of disease that we can follow,” says Tabet.

In contrast, common chronic diseases such as diabetes and heart diseases are potentially caused by a myriad of genetic variations as well as environmental and lifestyle factors. Developing gene therapy for these conditions would be much more complex, but researchers hope that the therapeutic advances in the rare-genetic-disease space may one day have broader applications.

Gene therapy is not a new field. As early as the 1960s, scientists began developing early concepts for gene therapy. In the decades since, researchers around the globe have been incrementally building insights in this area, but a recent challenge has been scaling up these therapies into a consistent product available to patients. Other challenges include designing therapies that avoid triggering an immune response and that are safe and effective.

Pfizer has a broad team of gene therapy and disease-area experts who, along with industry and academic collaborators, are working at every stage to overcome these scientific challenges. In addition, Pfizer has made massive investments in scaling up its gene therapy manufacturing capabilities.

“To make a very consistent gene therapy product at large scale requires significant expertise,” says Pan. “We have a heritage of over 30 years making very complex biologics. And we have tools with which we can analyze the final product down to the atomic level, so we know exactly what we’re making,” he adds