A silver bullet for cancer? Scientists are using CRISPR to unlock patients’ true tumor-fighting potential
Scientists have tailored DNA-editing technology to boost the way the body fights cancer cells – a potential breakthrough.
They modified patients’ genes to instruct cancer-fighting cells to attack tumors using CRISPR, which is given as a single injection.
CRISPR has previously been used in humans to remove specific genes to make the immune system more active against cancer.
But the new study was able to not only remove specific genes, but insert new ones that program immune cells to fight the patient’s specific cancer.
dr. Antoni Ribas from the University of California, Los Angeles and one of the leaders of the study said: ‘This is a step forward in the development of personalized cancer treatment.’
Scientists at pharmaceutical company PACT Pharma used gene editing technology to isolate and clone immune cells from cancer patients and prepare them to target 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 targeted specifically at the cancer plaguing their bodies.
They are modified to be able to target each patient’s specific tumor, which has hundreds of unique mutations.
One month after treatment, five participants had stable disease, meaning their tumors had not grown.
The CRISPR tool consists of two main actors: a guide RNA and a DNA-cutting enzyme. A guide RNA is a specific RNA sequence that recognizes the target piece of DNA to be edited and directs the enzyme, Cas9, to begin the editing process.
Cas9 precisely cuts the target DNA strands 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 cut – 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, which can result in genetic changes, the Crispr system causes a mutation at a precise location in the genome.
When the cellular machinery repairs a DNA break, it removes a small piece of DNA. In this way, researchers can precisely exclude certain genes in the genome.
Scientists design a guide RNA that mirrors the DNA of the gene to be edited, known as the target.
The guide RNA combines with the Cas9 enzyme and guides it to the target gene. When the guide RNA matches the DNA of the target gene, Cas9 splices the DNA, turning off the target gene.
Because the CRISPR technique has been around for ten years and remains at the center of ambitious scientific projects.
Doctors are now investigating its use in the treatment of rare diseases and genetic disorders such as sickle cell disease.
‘The generation of personalized cell therapy for cancer would not be feasible without the newly developed ability to use the CRISPR technique to replace immune receptors in clinical cell preparations in one step,’ added Dr. Ribas.
The findings give hope 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 about 269,000 cases expected this year.
However, the technology is relatively new and raises some difficult ethical questions about its application for genetic modification.\
Medicine has entered an unexplored area where hereditary difficulties in the embryo could eventually be fixed.
Safety issues in gene editing technology research are not unheard of.
There is a risk of erroneously changing DNA or RNA in non-target regions, which could result in 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 birth to make them resistant to HIV.
His work on manipulating the genes of human embryos was deemed ‘monstrous’, ‘unethical’ and ‘very dangerous’.
A group of over 100 scientists in China condemned He’s work in 2018: ‘Conducting direct experiments on humans can only be described as madness.’
The group added: ‘Pandora’s box is open. We may still have a glimmer 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. Instead, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily undertake not to authorize any use of clinical germline editing unless certain conditions are met.’
PACT Pharma’s findings were Published Thursday in the journal Nature.