What’s the Big Deal About Gene Therapy?
2017/18 could well turn out to be revolutionary in
Table of Contents
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.
Kymriah and Yescarta
Leber’s congenital amaurosis (LCA) is an inherited disorder causing progressive blindness, associated with a mutation in the RPE65 gene. Enter
13-year-old patient Jack Hogan was the first recipient of post-approval Luxturna, in March 2018; his surgery was performed by
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.
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.
- Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013). Genome engineering using the CRISPR-Cas9 system. Nature protocols, 8(11), 2281.
- 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.