The Future of Medicine Is In Your DNA

On September 14th, 1990, 4-year-old Ashanthi De Silva became the first person to receive gene therapy for severe combined immunodeficiency (SCID). Her case kick- started a wave of research that spanned the 1990s, 2000s, and 2010s. Today, De Silva is living a rich, fulfilling life and is an advocate for gene therapy within the rare disease community. With a rapidly growing, multibillion dollar market of billions of dollars, gene therapy will change the lives of thousands of people and alter the face of personalized medicine forever. The question is, how?

DNA is the material that determines our physical characteristics. Defects in our DNA, called mutations, can lead to illness, disability, or death. Gene therapy is the process of modifying genetic material to treat or prevent disease, including adding, editing, or silencing genes.

Way back in the 1960s, scientists had speculated that DNA could be inserted into cells to cure genetic disorders. Ashanthi De Silva had a mutant ADA gene that caused her T-cells to die off, making her prone to bacterial infections. On that fateful day in 1990, doctors introduced a healthy gene into her body, which was successful in restoring the ADA gene’s function. After De Silva, other research continued, but doctors discovered that gene therapy can trigger severe side effects, including fatal immune responses and cancer.

Side effects can occur due to the biological processes underpinning gene therapy. The easiest way to insert a gene into a person’s cells is using viral vectors. Certain viruses work by entering a cell, inserting viral or disease-causing DNA into the cell’s host DNA, which produces mRNA that can code for disease-causing proteins. Gene therapy repackages this technology in the viral vector, using the technical mechanism of viruses but replacing the disease-causing viral DNA with a healthy, disease-eliminating gene.

However elegant this mechanism is, it poses a risk to the body. The body can perceive the viral vector as an actual virus and may attack the carrier, which can cause a severe reaction. Since actual viruses can target multiple types of cells, the viral vector could target the wrong cell and damage perfectly healthy cells. Another major source of risk is the possibility of cancer – viral vectors could activate oncogenes, or cancer-causing genes.

These risks were seen in the 1990s as gene therapies began development, and halted the progress of gene therapy until the 2010s. In the 2010s, new viral vectors were developed that were more regulated. This technology allowed the viral vectors to be specific about which cells they were targeting, when they needed to turn off or on, and tweak genes more precisely. In addition to improved viral vectors, another form of gene therapy was developed called gene editing. Gene editing allows tools such as CRISPR/CAS9 to actually cut away the defective gene and paste in a new healthy DNA sequence. A major area of recent research is the ability to use CRISPR/CAS9 to target even smaller portions of genes or individual nucleotides.

Another major area of study is stem cell research, where cells that are not yet differentiated into specific cells can be edited to carry healthy genes as they grow into their final form. Today, most gene therapies fix genes outside the body and then insert the new cells into the body (ex vivo). Research is increasing on in vivo trials, where cells are edited inside the body.

Gene therapy has since become a promising new form of treatment, with more financial backing from regulatory bodies and an increasing number of clinical trials dedicated to new treatments.

2025 saw some massive wins in gene therapy, including the first-ever CAR T-cell therapy for marginal zone lymphoma (a type of rare, slow-growing lymphatic cancer that presents about 7000 new cases a year). The FDA approved Breyanzi in December 2025, a drug that genetically modifies a patient’s T-cells to destroy cancer cells. Breyanzi is recommended for patients who have failed other prior treatments or have relapsed, which previously resulted in lower survival rates. The drug is life-changing: after treatment, 62.1% of patients showed no signs of lymphoma in their scans – a complete response.

Another breakthrough treatment includes Waskyra, the first gene therapy for Wiskott-Aldrich Syndrome (WAS, a very rare inherited immune disorder that affects about 1 in

100,000 people, mainly boys). Patients experience bleeding, eczema, recurrent infections, and increased immunodeficiencies. Until the FDA approved Waskyra, the only treatment for WAS was symptom management or early blood transfusions.

Waskyra works by genetically correcting the patient’s blood stem cells, which are then reinfused into the patient and restore protein function. Waskyra reduced the rate of severe infections by 93% and moderate to severe bleeding events by about 60%. This life-changing treatment allows patients to participate in everyday activities with less pain and fear.

That’s not all. 2025 also saw:

• The first cellular therapy to treat patients with severe aplastic anaemia (a rare disorder in which the bone marrow does not produce enough red blood cells)

• The first gene correction for RDEB (a life-changing skin disorder)

  
  

Additional research is underway into RNA therapies and DNA therapies. Some of the most active disease areas include blood disorders like sickle-cell disease, neurological disorders such as Parkinson’s and ALS, and metabolic disorders. Clinical trials are prioritizing safety after learning from historical mistakes, and diseases and cancers that were once incurable have had therapies developed that have greatly improved the lives of patients.

Though gene therapy is advancing in leaps and bounds, it is costly due to the complicated nature of the biological mechanism and the custom or mass manufacturing of viral vectors. Additionally, trials are strictly regulated inside very few clinical-grade facilities, and new therapies can take years to meet safety standards. Ethical questions are also raised, as gene therapies permanently alter a person’s biology, and the question of access and patient consent looms large.

Gene therapy can offer life-changing relief for those who previously had no options available. The next decade will likely see more breakthroughs that could make gene therapy a standard form of care. Ashanthi Dde Silva was the first to be treated with gene therapy, but by the end of her lifetime, she will be just one of many.