Followers of science and health news, particularly those with a terminal illness, may get the impression that the dawn of a new, disease-free era is upon us — and nowhere is this idea more evident than in the latest buzzword in the health sciences, CRISPR.
With this tool, a form of genetic engineering, scientists can edit a genome — that is, alter a set of genes among the tens of thousands contained in an organism's DNA. With CRISPR, scientists may have the ability to remove or correct disease-causing genes or insert new ones that could theoretically cure disease, including cancer.
But the technology comes with both potential benefits and risks. [10 Amazing Things Scientists Just Did with CRISPR]
Two important CRISPR studies published this month underscore the promise and concerns. The first, from a multi-institute team led by researchers at the University of California, San Francisco (UCSF) and published in the journal Nature, revealed a new, more efficient way of making changes in the genome using CRISPR. This method, which uses electrical fields, drew widespread praise from the biomedical research establishment, as relayed in numerous news reports.
The second study, from the laboratory of Allan Bradley at Wellcome Sanger Institute in England, published a few days later in the journal Nature Biotechnology, suggested that CRISPR gene editing may be doing more damage than scientists thought.
So, what's going on? And how close are scientists to actually using CRISPR to effectively treat cancer?
CRISPR getting crisper
CRISPR is one tool among many in the 40-year-old field of genetic engineering, storming onto the scene in 2012. The technology offers unprecedented precision in editing the genome — that is, opening up a strand of DNA and correcting an error typed into the genetic code. CRISPR is not the first method for editing genes, but it seems to be the most precise so far.
Here's how it works: CRISPRs, short for clustered regularly interspaced short palindromic repeats (don't worry — most scientists can't remember this), are stretches of DNA found in bacteria and other microbes. These microorganisms use CRISPRs to find and remove viral DNA that has invaded their genomes. It's a host defense system. The CRISPRs and associated proteins, such as Cas9, essentially snip out the viral DNA and patch things up.
The technology is just now entering the realm of clinical application, with still only a handful of patients receiving the treatment, all starting in 2017. However, CRISPR is used now — broadly and remarkably successfully — in creating laboratory animals and cell lines with key genetic characteristics that help scientists better study human diseases.
In this regard, part of the CRISPR promise has already been realized in terms of "really advancing the landscape of research in biomedicine in a way nobody thought possible," said Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences in Seattle, who uses CRISPR and other methods to edit human genes in the lab. [7 Diseases You Can Learn About from a Genetic Test]
And as for the other promise, clinical application, "There's really good news on the horizon," Urnov told Live Science.
CRISPR advances — and pitfalls
For CRISPR to work, the short strands first need to get into the nucleus of a cell, where DNA is found. To transport CRISPRs there, scientists use modified viruses, a decades-old delivery method. These harmless viruses invade the cell, as they are wont to do, and deposit the package. But manufacturing these viruses in significant numbers for clinical use can take months or a year, and critically ill patients usually don't have that long to wait.
That's why the new Nature article elicited such excitement and praise. In that work, scientists used electrical stimulation, not viruses, to ferry genetic material into the cell nucleus. This is called "electroporation," and it shortens the process to a few weeks. The method could greatly speed research efforts.
But the other new study, though it didn't reference the research on electrical stimulation, warned that CRISPR remains rife with danger. The technique can alter more parts of the DNA than scientists realized, including those parts located farther away from the region targeted by CRISPR, the researchers said.
In short, CRISPR can snip too much, and depending on what's snipped, this inaccuracy could spell trouble, the researchers wrote. Scientists using CRISPR might inadvertently cut out a cancer-suppression gene, for example.
And these errors could occur regardless of the ferry mechanism used, whether electroporation or viral vector, lead study author Michael Kosicki, a graduate student at the Wellcome Sanger Institute in England, told Live Science.
But Urnov, who wasn't involved in either study, said that he cautioned against drawing broad conclusions from the second paper. That study used mouse cells, not clinic-grade human cells, and did not use a CRISPR-Cas9 strain engineered for clinical use, he said. You can't compare the off-target cleavage seen in the mouse DNA to what might happen in the human studies, he added.
In the U.S. and Europe, no clinical trial would begin without passing through "rigorous safety review," Urnov said.
There are two primary safety concerns: 1) making sure the genetic change was made correctly, without snipping other regions, a danger that the second study highlighted and 2) ensuring the genetic change of interest, even if done correctly, is safe and that its alteration or removal has no unforeseen ramifications.
What cancer patients need to know
CRISPR has the potential to revolutionize cancer therapy, chiefly in the realm of immunotherapy. In cancer immunotherapy, the treatment genetically engineers immune cells called T cells to find and kill cancer cells, as if they were a cold virus. In 2017, the U.S. Food and Drug Administration approved two drugs for a type of immunotherapy called chimeric antigen receptor (CAR-T) immunotherapy. Neither treatment involved CRISPR, though.
But doctors worldwide are using both traditional immunotherapy and new CRISPR techniques to increase the number of cancer types that they can treat reliably, albeit all at the preliminary experimental level.
If you are cancer patient, the first thing you need to realize is that you don't necessarily want to be in need of these experimental therapies. If you do need one, that means the conventional treatments — chemotherapy, radiation and surgery — have failed. [7 Side Effects of Cancer Treatment, and How to Cope with Them]
The second thing that cancer patients must understand is that experimental CRISPR treatments are, well, experimental and not available to many. These treatments are offered primarily at research hospitals, and they don't work for the majority of patients. Doctors in those settings are trying to figure out if and how these therapies work, or how they need to be tweaked, so these physicians need to recruit patient-volunteers who have well-defined cancer types.
So, this is the key question: How close are we, really, to curing cancer with CRISPR? Of course, no expert can say for sure. Urnov said that he is confident that CRISPR technology will bring about more and more cures to a broad range of diseases, including certain cancer types, in the next few years.
Dr. Alexander Marson of UCSF, senior author on the electroporation study, suggested that we may get an answer about CRISPR's cancer applications rather soon. His team hopes to treat siblings who have an autoimmune disease so rare that it lacks a name. These patients' T cells have already been corrected using the non-viral gene-targeting method in the lab. The goal is to transfer corrected cells back into the children to treat their disease. Important work remains ahead to develop clinical-grade corrected cells, test their safety and seek regulatory approval, Marson told Live Science.
Marson and other members of this team also are partnering with the Parker Institute for Cancer Immunotherapy in San Francisco to engineer cells to treat a variety of cancers, now that CRISPR-mediated immune cell reprogramming can be done so effectively without relying on viruses.
This, hypothetically, would quicken the pace of CRISPR's entry into clinical studies and arrival as a mainstream treatment.
Follow Christopher Wanjek @wanjek for daily tweets on health and science with a humorous edge. Wanjek is the author of "Food at Work" and "Bad Medicine." His column, Bad Medicine, appears regularly on Live Science.