Scientists have adapted DNA-editing technology to speed up the way the body fights cancer cells, in a potential breakthrough.
They modified patients’ genes to instruct cancer-fighting cells to swarm tumors using CRISPR, which is given as a single injection.
CRISPR has previously been used in humans to knock out specific genes to allow the immune system to become more activated against cancer.
But the new study was able not only to remove specific genes, but also to insert new ones that program immune cells to fight a patient’s specific cancer.
Dr. Antoni Ribas, from the University of California, Los Angeles and co-leader of the study, said: “This is a major advance in the development of personalized cancer treatment.”
Scientists at the pharmaceutical company PACT Pharma used gene-editing technology to isolate and clone immune cells from cancer patients and prepare them to detect mutations in cancer cells.
The researchers took blood and tumor samples from 16 patients with various forms of cancer, including colon, breast and lung.
They isolated immune cells that had hundreds of mutations specifically targeting the cancers plaguing their bodies.
These were modified to be able to target each patient’s specific tumor, which has hundreds of unique mutations.
One month after treatment, five of the participants experienced stable disease, meaning their tumors had not grown.
The CRISPR tool consists of two main players: a guide RNA and a DNA-cutting enzyme. Guide RNA is a specific RNA sequence that recognizes the target piece of DNA to be edited and directs the enzyme, Cas9, to start the editing process.
Cas9 precisely cuts the target strands of DNA and removes a small piece, causing a gap in the DNA where a new piece of DNA can be added.
HOW DOES CRISPR WORK?
Crispr technology precisely changes small parts of the genetic code.
Unlike other gene silencing tools, the Crispr system targets the source material of the genome and permanently shuts down genes at the DNA level.
The DNA cleavage, known as a double-strand break, closely mimics the types of mutations that occur naturally, for example after chronic sun exposure.
But unlike UV rays that can cause genetic alterations, the Crispr system causes a mutation in a precise place in the genome.
When the cellular machinery repairs the DNA break, it removes a small piece of DNA. In this way, researchers can precisely turn off specific genes in the genome.
Scientists design the guide RNA to mirror the DNA of the gene to be edited, known as the target.
The guide RNA associates with the Cas9 enzyme and guides it to the target gene. When the guide RNA matches the DNA of the target gene, Cas9 cuts the DNA and turns off the target gene.
Since the CRISPR technique has been around for about a decade and is still at the center of ambitious scientific projects.
Doctors are now exploring its application in the treatment of rare diseases and genetic disorders such as sickle cell disease.
‘Generating a personalized cell treatment for cancer would not have been feasible without the recently developed ability to use CRISPR to replace immune receptors in clinical-grade cell preparations in a single step,’ added Dr Ribas.
The findings give hope to the 1.9 million Americans who will be diagnosed with some form of cancer this year.
Approximately 290,000 women and 2,700 men will be diagnosed with breast cancer, making it the most common cancer diagnosis.
Prostate cancer is the leading cancer diagnosis among men and the second most common diagnosis overall with around 269,000 cases expected this year.
Still, the technology is relatively new and raises some important ethical questions about its application for genetic remodeling.
Medicine has entered uncharted territory where inherited disabilities in an embryo could possibly be eliminated.
Safety issues in gene-editing technology research are not unknown.
There is a risk of mistakenly changing DNA or RNA in regions other than the target site, which could lead to unwanted side effects not only in the patient but also in future generations.
A major scandal rocked the world in 2019 when Chinese scientist He Jiankui was jailed after modifying the DNA of twins Lulu and Nana before they were born to make them resistant to HIV.
His work to manipulate the genes of human embryos was deemed “monstrous”, “unethical” and “highly dangerous”.
A group of more than 100 scientists in China criticized He’s work in 2018: “Performing direct human experiments can only be described as insane.”
The group added: ‘Pandora’s box has been opened. We could still have a ray of hope to close it before it’s too late.
In 2019, a group of scientists proposed a worldwide moratorium on human germline editing.
They wrote: ‘By ‘global moratorium’, we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, retaining the right to make their own decisions, voluntarily commit not to approve any use of clinical germline editing unless certain conditions are met.’
The PACT Pharma findings were published Thursday in the journal Nature.
