How CRISPR may Change Medicine
With the advent of CRISPR, a new way to edit DNA, the field of genomic technology has never been more exciting. The implications have yet to be seen, but scientists could theoretically snip out a person’s genetic risk for disease. However, it’s also never been a more anxiety-inducing time. Some experts argue that innovations in genomics are moving forward at a pace faster than our ability to parse their potential consequences.
CRISPR Gene Editing Is Being Tested in Human Patients, and the Results Could Revolutionize Health Care
It has only been seven years since scientists first discovered how to precisely and reliably splice the human genome using CRISPR, a tool that has the potential to snip out disease-causing mutations and cure genetic diseases such as sickle cell anaemia, certain types of cancer, and even blindness.
Doctors are eagerly exploring ways to utilize this relatively new technology in patient treatment. In November of last year, scientist Jiankui He shocked and concerned the scientific community by announcing that he had already used CRISPR to permanently modify the genomes of twin girls, making them immune to HIV infection. However, many experts believe that the safety and effectiveness of CRISPR in human patients have not been adequately proven. He’s experiment received criticism because he edited the embryos, resulting in every cell of the twins being changed, including their reproductive cells. This means that their edited genomes could be passed on to future generations, with uncertain long-term effects.
Recently, Editas Medicine and Allergan announced a more acceptable form of gene editing that targets genetic defects in cells not passed on to the next generation. They are enrolling patients with congenital vision diseases in the first U.S. test of whether CRISPR can correct a mutation in living human cells. Other ongoing trials, such as the one by partners Vertex Pharmaceuticals and CRISPR Therapeutics, focus on treating blood diseases by modifying cells outside the patient’s body and reintroducing them, with the goal of outnumbering the diseased cells within the body.
In the Editas study, CRISPR will be directly introduced into the eye to repair genetic mutations in the patients’ vision cells and potentially cure their disease. The specific illness being targeted is Leber congenital amaurosis 10 (LCA10), which is caused by a single mutation in the CEP290 gene. This gene is essential for building the outer portion of photoreceptor cells responsible for sensing and translating light into signals that travel to the brain through the optic nerve. The mutation hampers the photoreceptors’ ability to sense light, leading to low vision or blindness.
The fact that LCA10 is a single-gene disease makes it an ideal candidate for early CRISPR therapies. Scientists can use CRISPR as molecular scissors to precisely cut the DNA at predetermined locations, particularly around the defective CEP290 gene, and remove it. By eliminating the mutation, the normal protein can be produced, allowing the photoreceptor cells to function properly.
“We are going in and cutting out the mutation,” says Charles Albright, Chief Scientific Officer of Editas. “Hopefully, that will restore the normal protein to normal levels and enable patients to sense light again, ultimately translating into vision.”
While scientists recognize the tremendous potential of CRISPR in targeting and removing abnormal DNA sequences, there are still significant concerns about the safety and effectiveness of CRISPR gene editing once it is applied in the human body. CRISPR has shown success in lab settings using human cells, but as with any technology, there are occasional glitches. Some studies have indicated that gene editing can occasionally result in incorrect splicing within the genome. Additionally, there are broader questions about the long-term and unforeseen effects of artificially editing the human genome.
The genetic editing in this study would essentially eliminate the mutation that these individuals were born with, and depending on the timing of the treatment, it could not only restore but potentially preserve their vision. Some children with this condition are born with limited sight that gradually deteriorates, leading to blindness. Consequently, Editas and Allergan plan to include children as young as three years old in the study if the initial doses prove to be safe.
The trial aims to provide valuable insights into the future of CRISPR-based therapies by addressing numerous questions. Observing the technique in patients will provide doctors with clearer information about dosing the therapy and identifying potential side effects. Albright mentions that the treatment will be administered during outpatient surgery, with the surgeon injecting the molecular gene editing machinery under the retina. The CRISPR components will be enclosed in a deactivated adenovirus specifically designed to deliver its splicing payload to photoreceptor cells. Albright assures that even if the CRISPR enters other cells, it is not biologically hazardous since the mis-coded gene exists only in the photoreceptor cells.
To evaluate the effectiveness of CRISPR, the research team will assess the patients’ vision using a specialized test for individuals with low vision. They will also record video footage of the patients navigating through a maze, avoiding obstacles, and following instructions, such as stop signs. Additionally, the scientists plan to employ imaging techniques to track whether the photoreceptor cells have been successfully rebuilt. A New Technique That Lets Scientists Edit DNA Is Transforming Science – and Raising Difficult Questions
Kathy Niakan’s laboratory at London’s Francis Crick Institute may be the size of a walk-in closet, but it holds immense potential in the field of science. Niakan is preparing to conduct a groundbreaking experiment using the technique known as CRISPR-Cas9. In this experiment, she will manipulate the DNA of a human embryo by injecting a specially prepared liquid, ultimately rewriting the embryo’s genetic code. However, Niakan’s objective is not to create designer humans; instead, she aims to understand the crucial DNA sequences necessary for normal human development.
This research alone is significant, but it represents just one aspect of the revolution in genetics ignited by CRISPR-Cas9. This technique, a mere four years old, has the potential to transform disease treatment, impact our food choices, and revolutionize energy production, transportation, and even the conservation of endangered species. Experts believe that CRISPR can be employed to reprogram cells not only in humans but also in plants, insects, and virtually any DNA on Earth. Recently, a related CRISPR technique that can edit RNA, responsible for gene regulation and expression, was developed by a scientist at MIT and Harvard’s Broad Institute, further expanding the possibilities of CRISPR.
While Niakan progresses with her work, scientists worldwide are exploring diverse applications of this powerful tool. At the University of California, Riverside, researchers are reprogramming yeast strains to convert sugars into biofuel components. A plant pathologist at Pennsylvania State University has successfully created a non-browning mushroom. Scientists at Temple University in Philadelphia have used CRISPR to remove HIV from human cells in the laboratory and living animals infected with the virus. The vision extends to creating high-yield milk-producing cows, enhancing the taste of tomatoes, and even resurrecting extinct species. In July, the National Institutes of Health (NIH) will provide recommendations on the first proposed clinical trial using CRISPR, targeting myeloma patients by modifying their blood cells and enhancing their cancer-fighting genes before reintroducing the edited cells.
Speaking with biologists, geneticists, or botanists reveals an unprecedented level of excitement arising from this groundbreaking advancement. Similar to how personal computers revolutionized technology after the era of giant mainframes, CRISPR promises to democratize the ability to enhance nature for scientists across various fields and expertise levels. Although previous DNA alteration techniques existed, they were costly and complex. CRISPR, on the other hand, is neither. Nobel laureate David Baltimore describes it as a “game changer” due to its simplicity and power.
It is fitting that the first experiment using CRISPR to edit human embryos will take place at the Francis Crick Institute, named after one of the scientists who unveiled the structure of DNA. Francis Crick and James Watson’s 1953 discovery revolutionized genetics by elucidating the structure of DNA and paving the way for researchers to unravel its mysteries. The completion of the Human Genome Project in 2003 provided researchers with another crucial tool, the blueprint to study the functions of our genes. Enzymes capable of splicing aberrant DNA emerged in the 1970 It turns out that the key to unlocking DNA editing was discovered inside a cup of yogurt. In 2007, a group of dairy scientists investigating why yogurt bacteria were frequently infected by taste-altering viruses made an intriguing observation. As they sequenced the genome of the Streptococcus thermophilus bacteria, they discovered repeated fragments of DNA that served as a genetic record of viruses that had infected the bacteria before. These repeated segments, known as clustered regularly interspaced short palindromic repeats (CRISPR), contained snippets of the virus’ genes. When the same virus attempted to reinfect the bacteria, it would bind to its matching section on the bacterial genome, triggering an enzyme to remove the virus, effectively protecting the bacteria from infection.
This discovery was crucial, as scientists realized that CRISPR could be utilized beyond bacteria in yogurt. In the summer of 2012, two research groups led by Jennifer Doudna at the University of California, Berkeley, and Emmanuelle Charpentier, then at Umea University in Sweden, teamed up to explore the potential of CRISPR. They discovered that an enzyme called Cas9 could act as molecular scissors when paired with a specific RNA sequence. By loading CRISPR with its matching RNA sequence, the Cas9 enzyme could cut out targeted sections of DNA. Doudna recalls the excitement and the possibility of creating a simplified engineered version of CRISPR.
CRISPR is already making significant advancements across various areas of biology. Some researchers even see its potential in addressing the issue of plastic waste. In Japan, scientists have discovered a bacterium that can slowly degrade plastic shopping bags. They are exploring ways to use CRISPR to enhance the plastic-degrading gene, potentially turning these microbes into efficient garbage-eating machines. In essence, if there is a genetic aspect involved, there is likely a scientist considering the use of CRISPR for it.
However, as CRISPR research accelerates and its applications expand, questions of ethics and potential risks arise. The biotech industry anticipates significant profits from CRISPR-based treatments, genetically modified animals like pigs, and even engineered mushrooms hitting the market. The rapid integration of CRISPR into various scientific fields is concerning to those who are familiar with its capabilities. Harvard’s George Church expresses his worries about the technology, emphasizing the need for public awareness and concern.
The national-security establishment also recognizes the implications of CRISPR. Infectious diseases can potentially be transformed into super strains with just a few DNA edits, posing a threat to unprepared populations. With the availability of CRISPR tools online, the engineering of deadly disease-transmitting mosquitoes or DNA-damaging viruses becomes theoretically possible, with devastating consequences for human populations.
For now, the consensus among experts is that using CRISPR to treat humans, including editing the genomes of eggs, sperm, or embryos that develop into human beings, is premature. Nonetheless, Niakan cautiously proceeds with the first authorized editing of a normal human embryo. Her objective is to gain insights into the early stages of human development. By selectively removing genes that previous research suggests are crucial for embryo development, she aims to identify the genes necessary for healthy embryos. The attempted repairs of the DNA after gene removal are expected to fail due to the drastic disruption.
Consequently, the gene will be unable to contribute to the embryo’s development, preventing its further progression. However, this failure will yield new knowledge that would be “technically virtually impossible” to acquire without CRISPR. The insights gained from these experiments could potentially aid in preventing miscarriages and help couples struggling with infertility to start families.
Niakan emphasizes the importance of transparency and involving the public in the conversation. She believes it is crucial to explain why certain genes are selected and why the study is being conducted. While most scientists may
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