The findings, published today in the journal Molecular Therapy and highlighted in the most recent issue of Nature, represent the first time researchers been able to correct a disease-causing gene in its natural location in the human genome using engineered transcription activator-like effector nucleases.
Epidermolysis bullosa (EB) is a skin disease caused by genetic mutations. Patients suffering from EB – primarily children - lack the proteins that hold the epidermis and dermis together, which leads to painful blistering and sores. The condition is often deadly. The University of Minnesota is an international leader in the treatment of EB and the research that has led to new treatment approaches.
In their latest work, Osborn and Tolar's team collaborated with genomic engineer Daniel Voytas, Ph.D., of the University of Minnesota's College of Biological Sciences, to engineer transcription activator-like effector nucleases (TALENs) that target the mutation and correct the error in the skin cells of patients with the disease. Researchers then reprogrammed these cells to make pluripotent stem cells that can create many different kinds of tissues. These amended cells were then able to produce the missing protein when placed in living skin models.
"These results provide proof of principle for TALEN-based precision gene correction, and it could open the door for more individualized therapeutics," said Osborn, an assistant professor in the University of Minnesota Medical School's Department of Pediatrics Division of Blood and Marrow Transplantation.
By using an unbiased screening method, researchers were able to take a comprehensive approach to TALEN-mapping. This strategy helped identify three other possible locations for future research and potential therapies.
"This is the first time we've been able to seamlessly correct a disease-causing gene in its natural location in the human genome using the TALEN-based approach. This opened up options we did not have before when considering future therapies," said Tolar, director of the University's Stem Cell Institute and an associate professor in the Department of Pediatrics Division of Blood and Marrow Transplantation.
The University of Minnesota Pediatric Blood and Marrow Transplant team, led by John Wagner, M.D. and Bruce Blazar, M.D., has pioneered bone marrow transplantation as the standard of care for severe EB. Tolar and Osborn hope that the individualized "genome editing" of patient cells will provide the next generation of therapies for EB and other genetic diseases.
Funding for this research was supported by grants from the Epidermolysis Bullosa Research Fund, the Jackson Gabriel Silver Foundation, DebRA International, the University of Minnesota Academic Health Center, Pioneering Unique Cures for Kids Foundation, Children's Cancer Research Fund, and the United States of America Department of Defense. The National Institutes of Health supports several authors through grant R01 GM098861 and the Director's Pioneer Award DP1 OD006862.
Masonic Cancer Center, University of Minnesota is part of the University's Academic Health Center. It is designated by the National Cancer Institute as a Comprehensive Cancer Center. For more information about the Masonic Cancer Center, visit http://www.cancer.umn.edu or call 612-624-2620.
The University of Minnesota Medical School, with its two campuses in the Twin Cities and Duluth, is a leading educator of the next generation of physicians. Our graduates and the school's 3,800 faculty physicians and scientists advance patient care, discover biomedical research breakthroughs with more than $180 million in sponsored research annually, and enhance health through world-class patient care for the state of Minnesota and beyond. Visit http://www.med.umn.edu to learn more.
Caroline Marin | EurekAlert!
Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences