What is the CRISPR/Cas9 System?
CRISPR/Cas stands for "Clustered Regularly Interspaced Short Palindromic Repeats / CRISPR-associated." These are specific DNA sequences in the genome that are recognized by CRISPR-associated proteins. CRISPR sequences were first discovered in bacteria in 1987, although their function was unknown at the time. It was later discovered that they form part of a bacterial immune system to fend off viruses. In 2012, scientists Jennifer Doudna and Emmanuelle Charpentier demonstrated how this system could be used in genetic engineering to specifically alter gene sequences. For this groundbreaking discovery, they were awarded the Nobel Prize in Chemistry in 2020. Neuroscientist Feng Zhang from MIT in Boston later adapted the system for use in mammalian cells and experimental animals.
How Does CRISPR Work?
The CRISPR-Cas9 system functions like molecular "scissors", enabling precise cutting of DNA at specific sites. It consists of two main components: an RNA molecule that recognizes a specific DNA sequence, and the Cas enzyme, which cuts the DNA at the targeted location. After the cut, the cell attempts to repair the damaged DNA, often introducing errors that disable the gene, or inserting a new, specifically designed sequence.
How and Where Is It Used?
CRISPR-Cas enables targeted and precise genome editing in bacteria, mammalian cells, and animal models. Compared to earlier methods, CRISPR-Cas allows for more precise, efficient, and cost-effective editing. For example, defective gene sequences can be corrected. In basic research, a gene can be inactivated to model a disease in cell cultures. For instance, researchers have used CRISPR-Cas to treat a metabolic liver disease in a mouse model (1).
Ethical Perspectives
Chinese scientist He Jiankui caused an international outcry in 2019 when he claimed to have edited human embryos in vitro to remove the receptor necessary for HIV infection—making them immune. He genetically modified germline cells, fertilized them in vitro, and implanted them in a uterus. As a result, the children born from this procedure carried heritable changes in their DNA. At the time, there was no ethics committee approval or appropriate research funding for the procedure. The risks were too uncertain. He was sentenced to three years in prison for illegal medical practices (2).
This incident triggered global calls for a moratorium. Today, many countries have strict legal and ethical regulations on the use of CRISPR-Cas in humans. In the European Union, editing of human germline cells—whose changes would be heritable—is largely prohibited.
Another controversy centers around intellectual property and commercial rights. A heated patent dispute emerged between Doudna and Zhang that has continued for years. The U.S. Patent Office ruled against the Nobel laureates and granted the patent to Zhang (3). In contrast, the European authorities recognized Doudna and Charpentier as the rightful patent holders (4).
Opportunities and Challenges
The opportunities that genome editing offers are undeniable. It significantly accelerates and simplifies basic research and unlocks previously unimaginable possibilities. In the clinic, for example, CRISPR-Cas has shown success in treating Leber’s congenital amaurosis, a rare eye disease. Promising results have also come from clinical trials targeting blood disorders such as sickle cell anemia and beta-thalassemia (5).
However, there are still several challenges. The CRISPR-Cas system can cause unintended changes in the genome—so-called off-target effects. To ensure the safety of CRISPR-Cas-based therapies, rigorous testing protocols are essential.
Because genome editing raises not only scientific but also ethical and societal questions, interdisciplinary collaboration is essential. Swiss researchers are playing a key role in establishing frameworks for such collaborations (6).
There is general consensus that the medical benefits of gene editing outweigh the risks, but further research and regulatory standards are still needed (7).
Sources
1. Villiger L, Grisch-Chan HM, Lindsay H, Ringnalda F, Pogliano CB, Allegri G, et al. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat Med. October 2018;24(10):1519–25.
2. Chinese scientist who produced genetically altered babies sentenced to 3 years in jail [Internet]. [cited May 14, 2025]. Available from: https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail
3. CRISPR's Nobel Prize winners defeated in key patent claim for genome editor [Internet]. [cited May 14, 2025]. Available from: https://www.science.org/content/article/crispr-s-nobel-prize-winners-defeated-key-patent-claim-genome-editor
4. transGEN [Internet]. [cited May 14, 2025]. Streit um CRISPR/Cas-Patente: Die unendliche Geschichte. Available from: https://www.transgen.de/recht/2721.crispr-streit-patent.html
5. Zhang S, Wang Y, Mao D, Wang Y, Zhang H, Pan Y, et al. Current trends of clinical trials involving CRISPR/Cas systems. Front Med [Internet]. November 10, 2023 [cited May 14, 2025];10. Available from: https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1292452/full
6. Kandlbinder A, Peter-Spiess MH, Leeners B, Mollaysa A, Cavazza T, Meier A, et al. Strategies for Interdisciplinary Human Gene Editing Research: Insights from a Swiss Project. CRISPR J. April 2025;8(2):79–88.
7. Joseph AM, Karas M, Ramadan Y, Joubran E, Jacobs RJ. Ethical Perspectives of Therapeutic Human Genome Editing From Multiple and Diverse Viewpoints: A Scoping Review. Cureus. 14(11):e31927.
