Imagine going to a store and being forced to purchase the same exact shirt as everyone who is your size. Or going to a restaurant where you have to order the same meal as everyone your age. Or going to a party and having to listen to the same music as everyone who has your hair color.
In reality, these things of course sound absurd. People are given a variety of choices because no two people are alike.
The same holds true for cancer. It doesn’t exist as a singular trait. It is comprised of its own tumor microenvironment that allows it to live and thrive.
The complexity of a single cancer tumor, at the current detectable limits of our most innovative technology, contains millions of cells with different functions, morphology, behaviors, and properties.
Then why don’t we have individualized options to treat each patient’s cancer? This is the very thing that scientists around the world are working to make a reality.
CRISPR and its Concerns
CRISPR is a novel technology that is being utilized as a tool to edit portions of DNA to artificially manipulate how cells, organs, and entire organisms function.
CRISPR is on the verge of being incorporated in personalized treatment, but early concerns of the technology hindered its early progress.
One of the biggest concerns with using CRISPR technology in humans is the possibility of off-target effects where the DNA is cut at a region different from the target gene.
Since CRISPR technology is capable of altering the DNA, off-target effects could be as simple as silent mutations that create no alterations in how the DNA is read, but it could be as catastrophic as initiating the degradation of healthy cells as well.
Another concern is that the CRISPR/CAS9 system elicits an immune response that could either render the treatment ineffective or cause adverse events in the patient.
Furthermore, the capability of editing the human genome for particular characteristics presents a major ethical concern as well. The line drawn between medical advancements and unethical practices can quickly become very gray when scientific tools become this revolutionary.
Innovative Advancements Strengthen Support for CRISPR
To mitigate these concerns, efforts are being implemented to optimize CRISPR/CAS9 systems. A major strategy with varied success is the utilization of delivery systems such as nanoparticles or viral vectors to improve the efficiency and accuracy of CRISPR/CAS9.
These delivery systems can help ensure that the CRISPR components reach the intended targets without affecting other non-targeted cells.
Genetically modifying CAS9 enzymes may also be an avenue for increased precision that is currently being tested.
Corrected safeguards and methods are continually being implemented to minimize these off-target effects seen in many past in vitro experiments using CRISPR.
“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced,” said Jennifer Doudna, one of the main contributors to discovering the technology contained gene editing capabilities.
Limitations of Current Cancer Treatments
Now, let’s transition to the field of healthcare and imagine everyone with your same generic health condition, such as cancer, receives the exact same treatment plan.
When a person is diagnosed with cancer, often times the individual has a portion of the tumor sequenced for gene/protein expression.
This is a way for the clinician to identify specific properties and mutations that have led to the malignancy in order to understand how the cancer is likely to behave and establish the best course for treatment.
Unfortunately, if targeted therapy doesn’t exist for their specific mutations in the cancer, broad-spectrum therapy such as chemotherapy may yield the best option.
These therapy options are used across all types of cancer and frequently lead to relapse and recurrence of the cancer in addition to a plethora of undesirable side effects.
CRISPR’S History
CRISPR was originally discovered in bacteria in 1987 by Yoshizumi Ishino and his team in Japan.
In bacteria, CRISPR exists as a natural segment of DNA that is utilized as a defense mechanism against viral infections. It wasn’t until 2012 that it was harnessed for its gene-editing capabilities by scientists George Church, Jennifer Doudna, Emmanuelle Charpentier and Feng Zhang.
They’ve discovered a way to couple CRISPR guide RNA with an enzyme known as CAS9 to be utilized as a gene-editing tool. The CRISPR/CAS9 system is capable of cutting DNA at specific regions to cause activation, silencing, deletion or insertion of genes into a genome of human cells.
The possibilities appear to be endless with the optimism of this new genetic engineering tool, but it still has a long way to go in order to maximize its potential in a safe and acceptable manner.
Jennifer Doudna has an optimistically cautious approach to the science she has helped develop with the following statement:
“Then, too, while gene editing is capable of repairing DNA in cultured human cells, it will be years before its efficacy is (or is not) demonstrated in human patients, and the few clinical successes that have been achieved so far with cancer immunotherapy and HIV might or might not be accurate predictors of other successes to come,” she wrote in “Crack in Creation: Gene Editing and Unthinkable Power to Control Evolution.”
CRISPR/CAS9 System for Personalized Cancer Treatment
In order to create a personalized cancer treatment, cross-disciplinary studies are being conducted to merge immunology with molecular biology.
CRISPR technology was recently used and published in Nature by Susan Foy and her team in a 2022 clinical trial to genetically engineer patients’ personal T-cells in an effort to weaponize the patient’s own immune system selectively against their specific cancer cells.
T-cells are a type of white blood cell in the adaptive immune system that play a vital role in eliminating foreign or mutated cells. Each T-cell is specific for a particular target antigen that is recognized by its own T-cell receptor (TCR).
The cancer patients’ T-cells were extracted, modified with CRISPR technology to alter TCRs for the targeting of their particular cancer, and implanted back in the patient to find and kill the cancer cells.
Unfortunately, the treatment was only effective in a small portion of patients.
Despite this fact, the study was successful in that knocking out native TCRs and knocking in new ones safely in a single-step process could be optimized to increase efficacy in solid tumor patients.
The Future of CRISPR
As long as scientists use CRISPR in a cautious and methodical way, they will find more positive uses for this technology. It’s of course simply a matter of keeping it in the hands of ethical scientists, most of whom play by the rules.
While skepticism remains prevalent for this new technology, scientists continue to make strides to improve the outlook and potential for it to be used positively and safely in cancer treatment.
