In hindsight, one could say the iPhone basically invented the smartphone market with its interactive touch screen, internet-surfing capabilities, app store, and camera. Except it didn’t. The LG Prada, released in 2006, had a camera, apps, a web browser, and the same type of touchscreen as the iPhone. LG had the technology right, but another company came along and simply did it better. A similar dynamic might now be playing out in the world of gene editing.
Although there are three main gene-editing tools being used today, CRISPR, which stands for “clustered regularly interspaced short palindromic repeats,” has become the most widely used due to its simplicity and versatility. One of the publicly traded companies using CRISPR to develop treatments for diseases is CRISPR Therapeutics (NASDAQ:CRSP). Despite the acceptance of CRISPR-Cas9 as the standard system for gene editing, new methods are being discovered that could make CRISPR Therapeutics’ Cas9 methodology the LG Prada of the gene-editing world.
Keeping your eye on the ball
Jennifer Doudna, a biochemist at the University of California, Berkeley, and Emmanuelle Charpentier, who headed a lab at the University of Vienna, first published evidence that CRISPR could cut targeted DNA in June 2012. But a patent filed seven months later by the Broad Institute of MIT and Harvard tried to undercut the pair’s exclusive claim to commercialize the approach by outlining a more specific description of the process in the cells that make up plants, animals, and humans.
Despite the dispute over patents and licensing revenues, Doudna and Charpentier won the 2020 Nobel Prize in Chemistry for discovering the gene-editing capabilities of bacteria using CRISPR-Cas9. Today, Doudna is associated with Intellia Therapeutics (NASDAQ:NTLA) and Caribou Biosciences, while Charpentier is associated with several companies including CRISPR Therapeutics. Another publicly traded company, Editas Medicine (NASDAQ:EDIT), was originally founded by Doudna, but is now associated with the Broad Institute patent claim.
While the battles in court continue to this day, other companies are finding new CRISPR tools that may be even more effective at editing genes in some circumstances. The foundational tool, CRISPR-Cas9, makes a blunt double-stranded DNA break. One drawback of this approach is a propensity to occasionally make cuts at unintended sites in the DNA. Although additional engineering has largely overcome this, it’s a frightening possible side effect. CRISPR-Cas12 was the next widely accepted tool. This method makes staggered cuts and can edit epigenomes — the chemical compounds that can tell genes to turn on or off. Cas13 influences gene expression by targeting RNA instead of DNA. However, more recent research has discovered CasX and CasY. CRISPR-CasX is smaller than Cas9 and can be used to control gene expression, not just to edit genes. CasY acts much like Cas9, but is made of a completely different protein structure, allowing it to function in different conditions.
New tech trying to leapfrog old tech
In 2017, Excision BioTherapeutics was the first to obtain an exclusive license for the new CasX and CasY gene editors from Jennifer Doudna’s lab at UC Berkeley. In March, the company used the Cas9 tool to successfully remove simian immunodeficiency virus (SIV) genomes from monkeys. SIV is an HIV-like virus that affects monkeys; removing the virus’ genome eliminates its ability to infect cells. Excision is also working on gene-based approaches for treating herpes and a rare central nervous system disease. And the company is applying the CasX and CasY tools for its work on hepatitis B and COVID-19, respectively. Other than its work on HIV, none of the company’s treatments are expected to start in clinical trials before 2022.
For now, CRISPR Therapeutics is safe. The company’s pipeline is currently targeting beta thalassemia and sickle cell disease — diseases caused by a single gene defect, ideal for the Cas9 approach — and multiple immune cell products designed to attack cancer cells. Despite the advances in new gene-editing methods, even Excision BioTherapeutics is relying on the Cas9 tool in most of its clinical studies.
Don’t get too comfortable
Investors in CRISPR Therapeutics and other gene-editing companies like Intellia Therapeutics and Editas Medicine shouldn’t get complacent. When investing, it’s easier to understand faster and cheaper technology in computing or consumer products. Just because these advances are in biology doesn’t mean the same rules won’t apply. Researchers will continue to find better and cheaper ways of manipulating genomes to treat and cure diseases. The fact that a small start-up managed to grab an exclusive license from the Nobel Prize-winning lab that practically invented gene editing should raise alarm. Savvy shareholders will look out for indications that the CasX and CasY tools are being applied in areas once assumed to be the domain of CRISPR Therapeutics’ and its Cas9 methods.