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Scientists have been making nanoparticles out of DNA strands for two decades, manipulating the bonds that maintain DNA’s double-helical shape to sculpt self-assembling structures that could someday have jaw-dropping medical applications.
The study of DNA nanoparticles, however, has focused mostly on their architecture, turning the genetic code of life into components for fabricating minuscule robots. A pair of Iowa State University researchers in the genetics, development, and cell biology department—professor Eric Henderson and recent doctoral graduate Chang-Yong Oh—hope to change that by showing nanoscale materials made of DNA can convey their built-in genetic instructions.
“So far, most people have been exploring DNA nanoparticles from an engineering perspective. Little attention has been paid to the information held in those DNA strands,” Oh said.
Women are more likely than men to have conditions such as lupus, rheumatoid arthritis, and autoimmune hepatitis (depicted above in a cellular micrograph), in which their immune response attacks healthy, functioning parts of their body. Yet the reason behind this sex-based imbalance has long eluded scientists. Now, a study published last week in proposes that a molecule associated with the X chromosome may be partly to blame. Researchers noticed that many of the proteins commonly targeted by the immune system in people with autoimmune diseases had something in common: They help a molecule called Xist carry out its function. Xist molecules act a bit like quality control inspectors for women’s extra X chromosomes, preventing them from producing a toxic amount of proteins. The scientists suspect that when immune cells encounter large bunches of these Xist-related proteins—for instance, when a dead cell spills them into the bloodstream—they may react by making antibodies to attack them throughout the body. To test the idea, the team studied genetically engineered mice in which both males and females produced Xist. Like their female counterparts, these males were also at an increased risk of developing severe cases of lupus. The researchers also found that people with autoimmune disorders had more antibodies for Xist-related proteins in their blood. Still, Xist molecules may not be the only factor at play: Experts note that some people produce these Xist-related antibodies without developing autoimmune disorders, reports.
A team of researchers at the Carl Gustav Carus Faculty of Medicine, TUD Dresden University of Technology, led by Prof. Frank Buchholz, has achieved a major breakthrough in genome editing technology. They’ve developed a cutting-edge method that combines the power of designer-recombinases with programmable DNA-binding domains to create precise and adaptable genome editing tools.
Traditional genome editing faced limitations in achieving ultimate precision until now. Prof. Buchholz’s team has broken through this barrier by creating what many have sought after: a zinc-finger conditioned recombinase. This innovative approach involves integrating a zinc-finger DNA-binding domain into specially designed recombinases. These enzymes remain inactive until the DNA-binding domain engages with its target site, adjacent to the recombinase binding area.
The significance of this achievement lies in the fusion of two key strengths: the targeting ease of programmable nucleases and the precise DNA editing capabilities of recombinases. This breakthrough overcomes existing limitations in genome editing techniques and holds vast promise for therapeutic gene editing and various biomedical applications.
Most approved gene therapies today, including those involving CRISPR-Cas9, work their magic on cells removed from the body, after which the edited cells are returned to the patient.
This technique is ideal for targeting blood cells and is currently the method employed in newly approved CRISPR gene therapies for blood diseases like sickle cell anemia, in which edited blood cells are reinfused in patients after their bone marrow has been destroyed by chemotherapy.
A new, precision-targeted delivery method for CRISPR-Cas9, published in the journal Nature Biotechnology, enables gene editing on very specific subsets of cells while still in the body—a step toward a programmable delivery method that would eliminate the need to obliterate patients’ bone marrow and immune system before giving them edited blood cells.
Some hereditary genetic defects cause an exaggerated immune response that can be fatal. Using the CRISPR-Cas9 gene-editing tool, such defects can be corrected, thus normalizing the immune response, as researchers led by Klaus Rajewsky from the Max Delbrück Center now report in Science Immunology.
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disease of the immune system that usually occurs in infants and young children under the age of 18 months. The condition is severe and has a high mortality rate. It is caused by various gene mutations that prevent cytotoxic T cells from functioning normally. These are a group of immune cells that kill virus–infected cells or otherwise altered cells.
If a child with FHL contracts a virus—such as the Epstein-Barr virus (EBV), but also other viruses—the cytotoxic T cells cannot eliminate the infected cells. Instead, the immune response gets out of control. This leads to a cytokine storm and an excessive inflammatory reaction that affects the entire organism.
A gene editing tool using a system known as CRISPR-Cas9 has recently been approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease. The drug is known as Casgevy and the media has hailed this treatment as a ‘cure’ for sickle cell anemia patients. While it is still unclear if the drug completely cures these patients, clinical trials show exciting efficacy.
Sickle cell disease is a genetic blood disorder affecting thousands of US citizens. Many of these patients are African American and Hispanic. In sickle cell disease, hemoglobin, a protein in red blood cells that helps carry oxygen throughout the body, is mutated. As a result, blood cells change shape in the form of a sickle, giving the disease its name. Unfortunately, the mutated cells cause disruption of blood flow and prevent other blood cells from delivering oxygen to the body. This disease is extremely rare and can lower the quality of life in patients. Previously, there were limited treatments options including transfusions and medications for pain management. However, Casgevy provides a new option to help treat the patient and relieve pain for over a year after a single treatment.
One-time treatment using Casgevy improved life quality for sickle cell patients. A single-arm trial was conducted at multiple health centers in adults and adolescents. These patients were screened for two vaso-occlusive crises (VOCs) which are described as severely painful events due to a lack of oxygen delivery from sickle cell blood cells blocking blood flow. The primary measure of success in the trial was the number of VOCs after treatment. In total, 44 patients received Casgevy and 33 were able to follow up and be evaluated. Of the 33 patients that made it through the trial, 29 of them did not experience any VOCs for 12 months. This is a 93.5% success rate based on the number of patients that were analyzed. All 44 patients were able to successfully undergo treatment without any graft rejection. In addition, researchers concluded that this treatment was not only effective, but safe with few side effects.
Engineers at MIT, Penn State University, and Carnegie Mellon University have devised a way to manipulate cells in three dimensions using sound waves. These “acoustic tweezers” could make possible 3D printing of cell structures for tissue engineering and other applications, the researchers say.
Designing tissue implants that can be used to treat human disease requires precisely recreating the natural tissue architecture, but so far it has proven difficult to develop a single method that can achieve that while keeping cells viable and functional.
“The results presented in this paper provide a unique pathway to manipulate biological cells accurately and in three dimensions, without the need for any invasive contact, tagging, or biochemical labeling,” says Subra Suresh, president of Carnegie Mellon and former dean of engineering at MIT. “This approach could lead to new possibilities for research and applications in such areas as regenerative medicine, neuroscience, tissue engineering, biomanufacturing, and cancer metastasis.”
Feng Guo, an associate professor of intelligent systems engineering at the Indiana University Luddy School of Informatics, Computing and Engineering, is addressing the technical limitations of artificial intelligence computing hardware by developing a new hybrid computing system—which has been…
A team of IU bioengineers are building the intersection of brain organoids and artificial intelligence, which could potentially transform the performance and efficiency of advanced AI techniques.
