As a toxicologist, I’m always thinking about the safety of the things we are exposed to, like new diets, the magic remedies, and cutting-edge therapies. I believe that, at times, the application of novel therapeutic approaches is advancing faster than our ability to determine their safety. When I read the abstract of the opening Plenary Lecture for the 2018 SOT Annual Meeting and ToxExpo by Dr. Matthew H. Porteus, Stanford University, I wondered, is this new technology safe? I wanted to listen to what Dr. Porteus had to teach us about genome editing as a therapy and its safe application in patients.
Dr. Porteus is a pioneer of the genome-editing stem cells technology. He began his presentation explaining how genome-editing stem cells technology works. It has two categories: the allogeneic which uses cells from a donor who’s a match to the patients and the autologous which uses a person’s own cells. Both types can be used to give the cell a new property or restore it. He also mentioned that in order to have high frequencies of editing, you need to have a good nuclease to cut the double-strand breaks in the DNA to insert the sequence you want and lots of donor cells.
The first problem they encountered with this new technology was that the target cells activated an interferon response against the edition machinery—this is what I mentioned before: we never know how cells and organs are going to respond to a foreign substance or compound. That is why applied research is super interesting because you learn a lot about how to deal with and solve problems when you want to apply the treatment to patients. They solved the problem of the immune response activation by delivering the CRISPR-associated protein-9 nuclease (Cas9) as a ribonucleoprotein molecule inside a virus.
Moreover, Dr. Porteus talked about sickle cell disease in which the body produces abnormally shaped red blood cells, leading to anemia and poor oxygenation of the organs and tissues. To cure this kind of disease, you need to kill the stem cells that produce the abnormal blood cells with chemotherapy and introduce the newly edited cells into the bone marrow, so the treatment right now is not completely innocuous. It would be interesting for scientists to try to develop a better way to eradicate the diseased cells instead of poisoning the entire body.
I like to hear these interdisciplinary talks because as a toxicologist, I enjoy finding the toxicology part of the topic that is been discussed—in this case, how can the treatment be safer for the patient?
For me, it was intriguing to learn that we can think of these genetically-engineered cells as living drugs, and it made me think how toxicologists could help to improve or decrease the toxic aspect of the therapeutic application.
This talk reminded me of two episodes of the Radio Lab podcast, episodes I would recommend to those interested in this topic. The first one talks about the CRISPR technology. I liked it because it explains the technology with terms everyone can understand. The second one tells the story of one bone marrow donor and the patient that received the donation and how their ideologies and beliefs didn’t need to be the same in order for someone to save someone else’s life.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.