Gene therapy, CRISPR, and gene editing are all terms that are beginning to appear more frequently in headlines, and the concept of manipulating DNA inside cells – once found only in science fiction – is now reality. In fact, gene editing is routinely done in labs around the world, with potentially transformative applications for medicine. In this post, we discuss what gene therapy is, what is new and exciting in the field, and why the technology could change the way we treat certain diseases.

What is gene therapy?

Gene therapy can be defined as making changes to the DNA inside of cells to treat disease. Each person is made up of trillions of cells, each with DNA that encodes about 25,000 genes. Sometimes, one or more of these genes is broken (mutated), which can lead to serious debilitating and devastating disease. Gene therapy can be used to either add a new, healthy copy of the gene, or repair the existing broken gene so it’s healthy again (called ‘gene editing,’ a type of gene therapy). ISSCR researchers describe some of their work in this area here.

How is gene therapy different than current treatments?

When researchers completed sequencing the DNA of the human genome in 2003, part of the hope was to identify genes that cause disease when they malfunction, so that one day scientists could potentially fix the underlying genetic causes of disease, rather than just treat its symptoms as many conventional therapies do. They envisioned a transformative field of medicine: gene therapy.

How does gene therapy work?

Whether using gene therapy to fix a broken gene or add a new healthy copy of that gene, new DNA must be inserted into cells. A common way that scientists add healthy DNA to cells is by using viruses — nature’s own DNA syringe. Viruses have evolved highly effective ways to inject their DNA (or RNA) into host cells; harnessing that same method for good, scientists can replace the harmful DNA found inside some viruses with healthy DNA that can help patients. When these modified viruses encounter a cell, rather than injecting them with harmful virus DNA, the virus inserts healthy DNA to repair or replace the broken gene. Genes can either be repaired inside the body by injecting the virus directly into the patient, or the cells can be removed first, repaired in a lab outside the body, and then transplanted back into the patient.

What technologies are used to find and repair genes?

Finding a broken or damaged gene can be a challenge. There are roughly 25,000 genes in each cell, but each gene can be made up of thousands of building blocks called ‘base pairs’, adding up to a total of 3 billion base pairs in each cell. How do scientists target one of 3 billion base pairs to fix the mutated gene?

Early pioneering technologies use designer proteins that act like DNA-cutting scissors capable of finding specific base pairs in the human genome and snipping DNA inside of cells, causing the gene to be repaired with healthy DNA. Over time, however, these proteins were found to be difficult and time-consuming to design, expensive, inefficient, and challenging to modify for new genes. In just the last five years, a new molecular scissor-based system, CRISPR, has become the breakthrough technology that has catapulted the efficiency and simplicity of gene editing to new levels, allowing scientists the flexibility to edit almost any part of the human genome with pin-point accuracy and ease, and at a fraction of the price. The CRISPR era has sparked real excitement among scientists worldwide.

Diseases actively being investigated as candidates for gene therapy

The first wave of gene therapy research is aimed at diseases that have clearly defined mutations within a single gene. These diseases include blood disorders, cystic fibrosis, skin disorders, muscular dystrophy, Hunter syndrome, and some degenerative eye conditions, among others. Gene editing can also help treat cancer by modifying the patient’s own immune system to target and kill cancer cells, known as CAR-T therapy.

Importantly, all gene therapies currently in clinical trials do not edit DNA in sperm or eggs, and therefore the changes made to the DNA will not be passed on to future generations.

Future possibilities

Gene therapy is a promising and exciting therapeutic approach, and may eventually be useful in treating many diseases, particularly when combined with stem cell technologies. Before it is routinely used in the clinic, however, important safety and health concerns need to be addressed. The most pressing concern is the accuracy and specificity of gene modifications; any unintended changes to the DNA could potentially introduce health risks. However, researchers are now aware of these concerns and are working hard to understand the issues involved and minimize the risk.

As they are developed, new and evolving technologies are granting scientists the ability to fix the once-inaccessible causes of many devastating genetic diseases – the genes themselves. With further rigorous testing and study, transformative gene editing therapies could potentially be on the horizon for several diseases for which there are currently no cures.