The discovery of genome-editing enzymes such as CRISPR-Cas9 has resulted in numerous efforts to develop new therapeutics to address genetic disease. That’s because the ability to make modifications to a patient’s genome holds tremendous potential. Unfortunately, potential might be all it has right now.
“There are a few barriers right now to this technology really hitting the mainstream,” said Ross Wilson, project scientist and principal investigator at the University of California Berkeley, California Institute for Quantitive Biosciences. “One of the main concerns is around safety, and a lot of work and testing is being done when these enzymes modify a genome to make sure they are not making unwanted modifications at the same time. The good news is these enzymes are making precise edits without unwanted effects. Another nice thing is scientists are developing new versions of these enzymes that are even better and even less likely to make unwanted changes to genomes.”
Another barrier to bringing CRISPR to the mainstream is related to the delivery of the therapeutic enzymes, which is the field Wilson’s lab is focusing on.
“It’s pretty easy to take human cells in a petri dish and modify them using these enzymes, because we can use a little electric shock to trick the cells into taking the enzymes inside,” Wilson said. “But this is the sort of thing that can’t really be done in a living patient. Cells are very savvy when it comes to what they let inside because they have to defend against viruses, for example. These genome editing enzymes look like a threat.”
Indeed, a major challenge is getting around the cell’s defenses and carrying out genome editing for efficient modification of cells within a patient. However, one type of therapy moving forward quickly is called autologous transplantation, essentially a patient making a donation to themselves.
“The way this works is you take out some blood cells from a patient and in the laboratory make a modification to those cells and then return these cells to the patient,” Wilson said. “One gene-based disease that could be cured this way is sickle cell disease. If you take a patient’s stem cells out, edit the genome in those cells, and transplant them back into the patient, you can cure the gene that is responsible for sickle cell.”
Therapies based on autologous transplantation will be the first to really take root, Wilson said.
“But this is a narrow window of therapies,” Wilson said. “If you wanted to reach the broadest number of patients you would need a way to edit the genome inside a living patient. That’s the second big barrier.”
Another barrier to this kind of genetic work is the level of understanding of the genetic foundation of different disease states.
“There are a lot of things people suffer from, like heart disease, for example, where a lot of genes may be working together to cause a poor outcome in a patient,” he said. “As medical research advances, we will have a better picture of what sort of things need to be edited to give people better outcomes. Our understanding of the interplay between our genes and our health is one of the things that will give us the most opportunity in putting gene editing therapy to use.”
Wilson will discuss precision medicine issues at the HIMSS and Healthcare IT News Precision Medicine Summit, June 12-13, 2017, in Boston, during a session entitled “How genome editing might reshape the medical landscape.”