What’s the Big Deal About Gene Therapy?

2017/18 could well turn out to be revolutionary in the history – and perhaps more so the future – of medicine. In August 2017, the US Food and Drug Administration (FDA) gave its first gene therapy approval to Kymriah for treatment of acute lymphoblastic leukemia. Just weeks later Yescarta was approved for non-Hodgkin lymphoma. By Christmas that year, Luxturna became the first ever in vivo gene therapy to be FDA approved. In March 2018, Luxturna was used successfully to treat a young patient, preventing him from imminent blindness.

Altering the Genome

Genes are the instructions for life, so to speak, providing the template for necessary proteins to form and go about their daily business: that is, keeping you alive. Variations within the genome (your complete set of genes) are the reason why all of us are different, both from the inside and on the outside. Sometimes, however, these variations can cause your body to react negatively – leading to genetic diseases.

The concept of altering the genome has been around since 1972, with the aim to modify or replace faulty genes with healthy ones. Hence treatment of genetic diseases was possible by targeting the source – the very DNA that codes for life. Once thought of as the perfect treatment – combining efficacy and specificity with safety and mild side effects – the hype for gene therapy died off due to clinical failures.


CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology actually came about from studying bacterial defense systems. Used to destroy the DNA of invading viruses, bacterial ‘CRISPR’ targets and cuts strands of DNA at very precise locations1. Once cut, the cell’s own DNA repair machinery is able to insert or delete base pairs from the gene, or even replace the segment with a brand new gene, changing its behavior.

In 2012, Jennifer Doudna and colleagues discovered CRISPR-Cas9, a new and improved cutting technique that was faster and cheaper to perform, with greater ease of design and higher efficiency2. Because of this, a whole world of opportunities was reopened. Before long, pharmaceutical companies started to discover hit compounds – or genes in this case – formed using CRISPR. These promising ‘gene therapies’ quickly progressed to pre-clinical and clinical trials with the support of regulatory agencies like the FDA.

Viruses are used as the vector (mode of transport) to deliver gene therapy treatments to the nucleus of the cell.

Gene Therapies

Kymriah and Yescarta

Tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) were FDA approved in 2017, both for the treatment of certain blood cancers. Their route of administration involves the extraction of a patients’ T cells from their blood, modifying them and then re-infusing them back inside the body. By altering the very genome of T cells, they are able to synthesize a receptor that allows them to target and kill cancer cells.

t cell adoptive transfer gene therapy diagram
End-to-end process of T cell adoptive transfer – how drugs like Kymriah and Yescarta work.


Leber’s congenital amaurosis (LCA) is an inherited disorder causing progressive blindness, associated with a mutation in the RPE65 gene. Enter voretigene neparvovec (Luxturna), the culmination of decades of hard work by scientists at Spark Therapeutics and doctors at the Children’s Hospital of Philadelphia. Luxturna delivers ‘normal’ copies of the RPE65 gene to the cells in the eye, which in turn allows for the production of proteins required for visual signaling. Undeterred by the cost of treatment (USD 425,000 per eye!) and the rarity of the disease, clinical trials went to completion. The result? Outcomes were so irrefutable that the FDA gave its stamp of approval, along with a priority review voucher for Spark.

13-year-old patient Jack Hogan was the first recipient of post-approval Luxturna, in March 2018; his surgery was performed by Dr. Jason Comander at the Massachusetts Eye and Ear hospital. Two months later, the improvements to his vision were clear. Altering the genome through gene therapy was possible.

spark therapeutics luxturna CRISPR gene therapy
A vial of Spark Therapeutics’ Luxturna.

Future of Genetic Engineering

Genetic engineering itself is not a new field – with genetically modified organisms (GMOs) a hugely beneficial product of agriculture and biotechnology research. However, gene therapies like Luxturna prove that it is possible to reverse the effects of a gene after it has expressed itself in an organism. It gives hope to patients with inherited diseases that cures are possible, that your genome does not necessarily define you.

Inevitably, the number of gene therapies sent for FDA approval will increase in the future. All around the world, pharmaceutical companies are increasing their investments in gene therapy research. The possibilities for the development of therapies for genetic diseases are immense, as every process in our bodies is governed by our genes. It won’t be long before the focus shifts to altering other aspects of the genome, such as improving physical appearances, muscle growth, even intellect. Captain America’s Super-Soldier Serum and the elixir of youth might not be too far down the list.

gene therapy clinical trials graph
Almost 2600 candidates for gene therapy have made it to clinical trials as of 2017. Of these, over 100 have progressed past phase III trials.

Update: In November 2018, Chinese scientist He Jiankui announced the world’s first successful human DNA editing experiment. The embryos of a pair of twins were altered, removing a gene that reduces the susceptibility of the babies to HIV. Because of the ethical issues involved, this sparked a global outcry about CRISPR technology and gene therapy. Read about ‘designer’ babies here.


  1. Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013). Genome engineering using the CRISPR-Cas9 system. Nature protocols8(11), 2281.
  2. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. science, 1225829.

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