What Is Gene Therapy?

March 25, 2020

3 min read

Ever since the complete sequencing of the entire human genome in 2003, scientists have been working to decipher and interpret the approximately 3 billion base pairs that are estimated to make 25,000 genes. These genes code for protein or RNA structures that control how everything works in a cell and how cells communicate with each other. While there is still much that we don't know, researchers have started to piece together how diseases develop on this molecular level inside cells. With this growing pool of genetic knowledge, scientists are taking a second look at gene therapy to treat — and cure — inherited diseases.

What is gene therapy?

Gene therapy is a medical treatment with the underlying goal to deliver a DNA piece into a patient's cells as a "drug" to fix a malfunctioning gene with the intent to cure disease. Gene therapy was first conceptualized in the 1970s, and several attempts have been made at the approach in the intervening decades with some success. However, it was only in the late 2010s that the field started to reliably demonstrate successful therapies. This gene therapy revival started with an FDA approval in 2017 to treat an inherited form of vision loss. By the end of the decade, at least 15 gene therapies have been implemented globally with at least 10 being approved for use in the United States to treat a variety of inherited diseases, viral infections, and cancer. Almost 400 clinical trials involving gene therapies are in progress.

Does gene therapy really work?

Gene therapy as a field had a rough start. The initial thought that as soon as we could identify a problem gene, we'd be able to immediately treat all kinds of diseases turned out to be way to simplistic. Just knowing the genes that make up a person, even having a general idea of what that gene does, doesn't usually translate to an easily adapted therapy. One of the biggest hurdles the gene therapy field has had to overcome is the identification of reliable protective casings that can get DNA into the desired target cells without being destroyed by our extracellular environments. Much like how a pill is structured, where the chemical compound to be consumed is coated with a polymer to protect the medicine from being destroyed in our acidic stomachs, a DNA piece also needs to be protected until it reaches its final destination. Until the 2010s, the main protective caging approach, called a vector, was an empty virus shell. Use of a viral vector in early studies had significant drawbacks, including issues with targeting and safety, particularly in eliciting toxicity and inflammatory responses. In fact, people were killed as a result of these side effects, putting the whole field of gene therapy onto uncertain ground for scientists and prospective patients alike.

Advances in the last decade have fixed the issues of earlier approaches. First, viral vector engineering has drastically improved, alleviating both the delivery and safety issues of viral casings. Second, non-viral vector approaches are growing in popularity. These approaches promise large scale production and low or no immune response with their use, making them an enticing tool. Leading the pack for viral alternatives is CRISPR-Cas9 gene therapy, which is widely anticipated to change the face of modern medicine.

Will we see gene therapies for more complicated diseases in the future?

Most gene therapies being studied today are being pursued for diseases with a single known malfunctioning gene target. Even for cancer gene therapies, which can be heterogeneous in nature, we're targeting cancers with clear problem genes. But that doesn't mean other diseases can't also be treated with gene therapy in the future. Many diseases, especially chronic diseases that form over time like heart disease and diabetes, are caused by a combination of different genes of which we know some but not all. What's more, even if we know a gene that should be targeted for fixing, we're not always sure how to fix it, as all genetic changes should be taken in context within the backdrop of each individual's underlying unique genome. That's because our cells are jam packed with the protein and RNA products of our genes, and they're constantly interacting with each other in different ways that make targeting them much more complicated. However, as our understanding grows for how each of those ~ 25,000 gene products looks, moves, and interacts with other cellular players, expect that our ability to treat and cure complicated diseases to grow as well.