What is Gene Editing & CRISPR Technology?
In this week’s article, we look at the relatively new technological advances in gene editing and CRISPR therapeutics, discuss some of their ethical implications, and explore the companies making strides with these technologies.
Understanding DNA
Before diving into the topic of gene editing, it is important to understand what deoxyribonucleic acid (DNA) is. DNA, which is located in the nucleus or mitochondria of the cell, is in nearly all cells in the human body. It is used as a code to store relevant information, acting as an instruction manual for making proteins in the body.
DNA is able to make replicas of itself, meaning that when our cells divide, a replica of the DNA is produced in the new cell which matches the one in the old cell. This also means that information coded in our DNA can pass from parent to child.
Along with providing instructions for proteins in the body, DNA significantly determines a person's physical characteristics such as height, eye color and hair color.
What is Gene Editing?
Gene editing is an all-encompassing term for treatments that allow scientists to change the DNA of a living organism. This could be through the alteration, addition, or removal of genetic material within the genome.
One of the first demonstrations of successful gene editing occurred when Professor William Szybalski was able to prove that adding DNA into an animal cell was able to correct a genetic mutation in 1962. Currently, genome editing is most frequently being utilized in a research lab setting to understand a variety of diseases, including sickle cell, cystic fibrosis, and more.
Since there are multiple animal species that share similar genes as humans — such as mice, which share 85 percent of our genes — much of the testing is done through editing the genomes of animals. Other animals commonly used for gene editing research include fruit flies, zebrafish, nematodes, sea urchins, and more.
What is CRISPR?
Discovered in 2012 by Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna, one of the most well-known gene editing technologies is CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats). This approach is unique, as it involves making a precise cut to the DNA with the Cas9 enzyme, then utilizing the body's natural DNA repair process to make a desired, permanent change to the DNA at the cut site.
Both RNA and a protein called Cas enzyme or nuclease are necessary for CRISPR/Cas9 therapies. The guide RNA (gRNA) is used to lead the Cas9 to viral DNA, effectively creating a double-stranded break in the DNA. In other words, the RNA acts as a GPS to locate the desired DNA location for the Cas nuclease to cut. During the body's natural repair, changes are made to the DNA by adding, deleting, or changing genetic material, depending on where the cut was made.
This system was adapted by researching the naturally occurring processes of bacteria when faced with a virus. These bacteria have been noted to create segments called “CRISPR arrays”, where they capture small parts of the virus’ DNA, inserting it into their own so they can remember the virus if they encounter them in the future. This memory allows them to rapidly produce RNA molecules that match the stored viral DNA sequence, which guide Cas9-like enzymes to the matching viral DNA to neutralize the infection.
There are two types of DNA repair pathways activated by CRISPR-Cas9 gene editing: non-homologous end joining (NHEJ) and homology-directed repair (HDR). NHEJ normally results in small insertions or deletions to the DNA, while HDR uses a homologous DNA template to repair the break. Although NHEJ is regarded as more efficient, HDR tends to be more precise and less frequent.
Somatic vs. Germline Cells
There are two different types of cells that human genome editing technologies can be utilized on: somatic and germline.
Somatic cells are non-reproductive cells, meaning that changes made to these cells through gene editing would not be inheritable by further generations. Some examples of somatic cells include skin, muscle, nerve, skeletal, and blood cells.
Germline cells, on the other hand, are reproductive cells such as egg cells and sperm cells. Genome editing done to these cells has the potential to be passed down from generation to generation. As we will explore further in the article, the long-term possibilities for this type of gene editing has led to multiple countries, including the United States, prohibiting federal funding for germline cell editing.
The Possibilities of CRISPR & Gene Editing
There are multiple clinical applications currently in human trials to discover treatments for a range of diseases like cancer, sickle cell disease, and inherited blindness from Leber’s congenital amaurosis.
A notable example of a similar gene therapy in practice is the successful treatment of leukemia in a young girl in the UK in 2015. Scientists engineered her immune cells (T cells) to better target and destroy cancer cells. This demonstrated the potential of gene therapy to treat diseases unresponsive to conventional methods by modifying the function of existing genes.
Although gene editing faces many technical and ethical challenges, it is a promising technology for the future of human health, disease prevention, and disease treatment.
Ethical Concerns of Gene Editing
As discussed above, gene editing is possible for both somatic (non-reproductive) and germline (reproductive) cells. Since edits to germline cells are inheritable, alterations to these cells would be passed down through multiple generations. This calls into question whether these alterations violate the consent of future generations.
Additionally, long-term effects of genetic manipulation have not been studied enough to know all the potential future consequences of a change made now. These combined concerns have led to the prohibiting of federal funding for germline cell editing, including in the United States.
Hypothetically, this technology could allow an individual to enhance desirable traits of themselves or their lineage. Many people question the ethicality of utilizing gene editing beyond disease prevention and treatment.
We also must consider cost applications. Gene editing therapies, including CRISPR, are typically very expensive, with a course of treatment seeing prices of as much as $3 million USD. This poses the future issue of life saving treatment being unavailable for large parts of the population, increasing the existing health inequalities between wealthy and poor populations.
From a technical standpoint, another concern regarding our current gene editing abilities is that genome editing tools are not guaranteed to cut in the correct spot. Due to the variability of results of this error, scientists do not yet fully understand risks posed by this lack of guaranteed accuracy.
Like any other new treatment, it will be crucial to consult with qualified experts and engage in ongoing discussions to fully understand the complexities and implications of gene editing technologies before pursuing them.
Companies Leading the Way
One of the first organizations that comes to mind when discussing gene editing is CRISPR Therapeutics. Their CRISPR/Cas9 therapy is currently approved in multiple countries for eligible individuals with transfusion-dependent beta thalassemia and sickle cell disease. In 2019, their patient data on a CRISPR-based investigative therapy was released, which would later be published in The New England Journal of Medicine.
Another organization of note in the gene-editing space is Intellia Therapeutics. They are currently sponsoring multiple treatments in clinical trials focused on treating transthyretin (ATTR) amyloidosis and hereditary angioedema.
Something that makes them unique is that they are focused on a full-spectrum approach, meaning they are researching both in vivo therapies for genetic diseases, and ex vivo therapies for immuno-oncology and autoimmune diseases. In vivo refers to therapies that are injected directly into the person or living organism receiving treatment, while ex vivo refers to changes made on genetic tissue that have been removed from the body that will be returned once changes have been made.
Current Treatments
In November of 2023, Vertex Pharmaceuticals announced the authorization of their therapy CASGEVY®, made in collaboration with CRISPR Therapeutics, by the United Kingdom MHRA. The treatment would later be approved by the FDA in December of the same year. It was the first CRISP-based therapy to be approved by the FDA, and is used to treat sickle cell disease and transfusion-dependent beta thalassemia.
The only other CRISPR therapy currently approved by the FDA is LYFGENIA™, which was approved on the same day as CASGEVY®, and is also used to treat sickle cell disease for individuals who are 12 or older. LYFGENIA™ was developed by Bluebird Bio.
The FDA has approved 36 gene therapies as of 2024, though not all of those are gene editing specific. However, the large number of treatments in clinical trials proves how promising this technology will be in the future.
A Flexible Solution to Make Strides in Gene Editing
As gene editing is a relatively new technology, it is critical that you have a flexible, process-minded solution that can scale with you from drug-discovery to full-scale manufacturing. At High Purity New England, a Getinge Company (HPNE), we have over twenty years of experience in producing our flagship, high-quality HPConnexx™ Single-Use Assemblies.
With a brand agnostic model, our assemblies can be customized to your unique needs, regardless of part, brand, or company. Our time-tested method of scaling with start-ups gives us the unique ability to adapt to new technologies and drug discovery processes, providing security in your process.
Want to learn more? Get started by talking to one of our experts about how we can start making your perfect assembly today at info@hp-ne.com, or visit our contact us page.
Exploring More Industry Trends
Interested in expanding your biotech and biopharma knowledge further? Explore our previous article in our industry trends series including: The Effect of Artificial Intelligence on Biopharma, What is Cell & Gene Therapy, The Evolution and Impact of mRNA, The Importance of Lipid Nanoparticles in mRNA, and The Evolution and Impact of Monoclonal Antibodies (mAbs).
Make sure to check back on our blogs page for additional articles related to industry products and trends.
Disclaimer: The information provided in this article is for general knowledge and discussion purposes only, and should not be used for medical or legal advice of any sort.
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About HPNE
As the industry needs grow, High Purity New England, Inc. continues to supply the biopharmaceutical industry with a range of innovative products, from drug discovery and development to fill-finish, including their flagship product, custom single-use assemblies, as well as pumps, sensors, bioreactor systems, storage and handling solutions and other single-use solutions. Along with their own manufactured products for the global market, they are also a distributor for more than 18 brands in North America.
