What’s the Big Deal About Gene Therapy?

The past few months have been 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 going blind.

Gene Therapy and CRISPR

Genes are the instructions of 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 the 1972, with the aim to modify or replace faulty genes with healthy ones so that genetic diseases can be treated or prevented at 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 hails from bacterial defense systems. “CRISPR” can be programmed in this way to target and cut strands of your DNA at precise locations1. Once the DNA is cut, the cell’s own DNA repair machinery can be utilized to add or delete sequences of base pairs, or to make changes to the DNA by replacing an existing segment with a customized one.

In 2012, Jennifer Doudna and colleagues published a new and improved ‘cutting technique’ utilizing CRISPR to do it faster, cheaper, with greater ease of design and higher efficiency2. With this advent a whole world of opportunities was reopened. It wasn’t long before pharmaceutical companies started to discover hits, quickly moving on 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.


Tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) were FDA approved in 2017, both for the treatment of certain types of blood cancers. The route of administration involves 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, it allows them to express a receptor that allows them to target and kill cancer cells.


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 works by delivering ‘normal’ copies of the RPE65 gene to the cells in the eye, which in turn allows for the production 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 with outcomes so irrefutable that the FDA gave its stamp of approval, along with a priority review voucher for Spark.


A vial of Spark Therapeutics’ Luxturna.

The first post-approval administration of Luxturna was performed successfully on March 20, 2018 on 13 year old patient Jack Hogan by surgeon Jason Comander M.D., Ph.D at the Massachusetts Eye and Ear hospital.

Future of Gene Therapy

Luxturna was such a giant milestone as it reversed a disease at its source, the little fault in the genome, so to speak. By showing the world that even inherited diseases could be cured, Luxturna is laying down the marker for other genetic diseases to be similarly studied and corrected. And this is definitely the case, all around the world an increasing number of pharmaceutical companies are putting research emphasis on gene therapies with almost 100 potential treatments progressing into phase 3 clinical trials.


Almost 2600 candidates for gene therapy have progressed through to clinical trials as of 2017.

In the future, this number is bound to increase with the sheer number of inherited diseases that currently lack treatments. It won’t be long before the focus moves to altering other aspects of the genome such as physical appearance, muscle growth, even intellect; Captain America’s Super-Soldier Serum  and the elixir of youth might not be too far down the list.


  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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