#dna #genetics #gattaca #editing

Behold, have researchers found a groundbreaking method to fight tumors? Could genome-edited immune cells finally provide a way to defeat cancer?

In a recent clinical trial, immune cells were modified by CRISPR gene editing to recognize mutated proteins specific to tumors. When released into the body, the cells could target and kill the specific tumor cells. This cancer research utilized gene editing and T-cell engineering.

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The trial involved 16 individuals who suffered from solid tumors (including breast and colon cancer). The results were published in Nature by Heidi Ledford and then presented on November 10, 2022 in Boston, Massachusetts at The Society for Immunotherapy of Cancer conference. The findings were later released in Scientific American.

According to Antoni Ribas, a co-author of the study and a cancer researcher and physician at the University of California, Los Angeles, ” It is probably the most complicated therapy ever attempted in the clinic.” He describes the process as “trying to make an army out of a participant’s own T cells.”

To begin the study, Ribas and his colleagues ran DNA sequencing on each patient’s blood sample and tumor biopsies. The goal was to identify unique mutations of the timer, but not present in the blood. Ribas notes that these mutations differ across different types of cancer, with only a few being shared. Then using algorithms, Ribas’s team predicted which mutations were the most likely to initiate a response from the T cells(a type of white blood cell that functions to notice and destroy irregular cells); however, immune systems rarely destroy cancerous tumors. With that being said, the team used CRISPR gene editing to insert designated t-cell receptors that recognized the tumor. Patients were given medication to reduce normal immune cells before the researchers infused the engineered cell.

Joseph Fraietta, who specializes in designing T-cell cancer therapies at the University of Pennsylvania in Philadelphia, describes the process as “tremendously complicated”, for some cases could take more than a year to complete in certain cases.

Each individual in the study received T cells engineered to target up to three sites, and after some time, the concentration of the engineered T cells was higher than the average T cells in the bloodstream near the tumors. A month after the treatment, five participants’ tumors had not progressed, and only 2 showed evidence of T-cell activity.

While the treatment’s effectiveness was limited, Ribas notes that a small dose of T cells was used at first and stronger doses would be proven more effective. Fraietta feels “The technology will get better and better.”

Although engineered T cells, also known as CAR T cells, were approved to treat certain blood and lymphatic cancers, CAR T cells only target proteins that are present on the surface of tumor cells, and According to Fraietta, no surface proteins have been discovered in solid tumors. Additionally, tumor cells may suppress immune responses by releasing immune-suppressing chemical signals and consuming local nutrient supplies to promote their rapid growth.

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Researchers are hopeful to engineer T cells to not only recognize cancer mutations but also to become more active in the vicinity of the tumor. Potential techniques include ” removing the receptors that respond to immunosuppressive signals, or by tweaking their metabolism so that they can more easily find an energy source in the tumor environment,” as Heidi Ledford, writes in her article. With advances in CRISPR technology, researchers anticipate revolutionary ways of engineering immune cells in the next ten years.

In AP Biology this year, we learn about the Immune system. This topic is specifically related to the adaptive, or pathogen-specific, Immune response. T Lymphocytes, or T cells for short, are a part of the cell-mediated immune response where T-cells can identify, and kill infected or cancerous cells, while also preventing reinfecting.

Cancer Detection Using CRISPR Gene Editing

By avacuole

On April 23, 2023

In Student Post

Currently, many are accustomed to invasive cancer diagnostic methods such as endoscopies, colonoscopies, and mammograms. Driven by the desire to discover new methods, a group of researchers from the American Cancer Society developed an alternative method, which is a significant contribution to cancer detection.

Utilizing CRISPR gene editing as their approach, the group of ACS researchers developed an easy-to-use mechanism for detecting small amounts of cancer in plasma. CRISPR gene editing is a method that scientists and researchers have been using to modify an organism’s DNA. CRISPR gene editing is often done for numerous reasons, such as adding or removing genetic material, creating immune defense systems, and repairing DNA. Their detection method also allows healthcare professionals in diagnostics to decipher between malignant and benign cancer-related molecules that they may discover.

CRISPR Gene-Editing

The first step that the researchers made to develop this approach was to design a CRISPR system that creates a manufactured exosome out of two reporter molecule fragments, which they cut. An exosome is a small vesicle that carries material such as lipids, proteins, and nucleic acids after branching out from a host cell. Exosomes are typically involved in detecting cancerous cells because they provide a glimpse into the host cell they branched out from. Therefore, cancerous cells are shown in their exosomes through biomarkers, like micro RNAs (miRNA). In AP Biology class, microRNAs are described as materials that bind to complementary mRNAs to prevent the translation from occurring. MiRNAs are a recent discovery, identified in 1993. It is now concluded that most gene expression is influenced by them, so the researchers made efficient use of miRNA in their experiment. The two fragments of the reporter molecule came together and interacted with the CRISPR’s materials.

Micro RNA Sequence

The researchers concluded that if the targeted miRNA sequence was evident in the combination, the CRISPR system they made would become activated and cut apart the reporter molecule. The researchers specifically targeted miRNA-21, which is often involved in cancer development. The researchers were able to detect miRNA within a combination of similar sequences and later tested their method on a group of healthy exosomes and cancerous exosomes. Their CRISPR system successfully differentiated between the healthy and cancerous exosomes, which makes this system effective for cancer detection. The researchers are confident that their CRISPR gene editing approach to cancer detection will make diagnosis easier on patients and a more efficient process overall.

Cas9/10

By marcochondria

On March 24, 2022

In Student Post

Gene editing sounds to most like an intriguing opportunity at the very least, if not a groundbreaking advancement in human development, however it does not come without any flaw. We are not living in “Gattaca”quite yet to say the least. One of the most common gene editing processes, CRISPR, is equipped with a relatively predictable flaw in particular; an error taking place at the molecular level that results in the wrong genome being altered than what had been intended, therefore leading to potentially dangerous or life altering mutations in said gene. A team of specialized professionals at the University of Texas at Austin decided to revamp a significant component used for the CRISPR gene editing process. Their new version of Cas9 reduces the chances of the wrong genome being manipulated by thousands. This is a figurative unicorn of scientific discovery, it is groundbreaking on top of groundbreaking, it is cloth cut from the fabric of similar discoveries that have changed the course of human history and still – it is only the beginning.

When there is an error in the way the genomes are adjusted, it is a rather simple explanation as to how, and even simpler when describing how the new version of Cas9 can fix it. When the letters making up the DNA’s structure are incorrectly assembled or mismatched, causing a lack of stability in the structure of the DNA itself. Due to this, Cas9 is not capable of making the necessary adjustments to the DNA in order to properly execute the procedure. The new version of Cas9 is far more capable and strong, meaning that it can in fact execute the procedure.

Although this new Cas9 is an answer to a previously inherent setback to gene editing, it doesn’t come without its own respective setbacks. A primary caveat to the increased accuracy of this Cas9 is that it works at a much slower pace than Cas9 that is naturally occurring.

There is a self awareness that seeps through this accomplishment to the people that set it in motion. Kenneth Johnson, a professor at the University of Texas at Austin and co-author of the study even says that this newfound tool “could really be a game changer” when it comes to further use of gene editing among the public. It is truly a tremendous feat conquered by this group of experts in the field of genetic engineering.

Ultimately, further advancements in genetic editing could very well change the human race and the world as we know it so long as quality time and effort is put into it, as seen with this study. With the incentive of the potential advancement of human kind as a whole, its anyone’s guess as to what could one day be possible.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #dna #genetics #gattaca #editing

In First, Scientists Use CRISPR for Personalized Cancer Treatment

Cancer Detection Using CRISPR Gene Editing

Cas9/10

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