Using the new gene-editing enzyme CRISPR-Cpf1, researchers at UT Southwestern Medical Center have successfully corrected Duchenne muscular dystrophy in human cells and mice in the lab.
The UT Southwestern group had previously used CRISPR-Cas9, the original gene-editing system, to correct the Duchenne defect in a mouse model of the disease and in human cells. In the current work, they used a new variation of the gene-editing system to repair the defect in both a mouse model and in human cells.
Image shows heart muscle that is missing the dystrophin molecule.
Credit: UT Southwestern
"We took patient-derived cells that had the most common mutation responsible for Duchenne muscular dystrophy and we corrected them in vitro to restore production of the missing dystrophin protein in the cells. This work provides us with a promising new tool in the CRISPR toolbox," said author Dr. Eric Olson, Chairman of Molecular Biology, Co-Director of the UT Southwestern Wellstone Muscular Dystrophy Cooperative Research Center, and Director of the Hamon Center for Regenerative Science and Medicine.
The research appears in the journal Science Advances.
CRISPR-Cpf1 differs from CRISPR-Cas9 in a number of key ways. Cpf1 is much smaller than the Cas9 enzyme, which makes it easier to package inside a virus and therefore easier to deliver to muscle cells.
"By either skipping a mutation region or precisely repairing a mutation in the gene, CRISPR-Cpf1-mediated genome editing not only corrects Duchenne muscular dystrophy mutations but also improves muscle contractility and strength," said co-author Dr. Rhonda Bassel-Duby, Professor of Molecular Biology and Associate Director of the Hamon Center for Regenerative Science and Medicine.
Duchenne muscular dystrophy is caused by a mutation to one of the longest genes in the body. When there is a DNA error in the dystrophin gene, the body doesn't make the protein dystrophin, which serves as a sort of shock absorber for the muscle fiber. Since there are numerous places in the dystrophin gene where a mutation can occur, flexibility for gene-editing treatment is crucial.
Duchenne occurs in about 1 in every 5,000 boys, according to the Centers for Disease Control and Prevention. Duchenne muscular dystrophy is a progressive disease affecting both muscle used for movement and heart muscle, with patients typically succumbing before age 30 due to heart failure.
"CRISPR-Cpf1 gene-editing can be applied to a vast number of mutations in the dystrophin gene. Our goal is to permanently correct the underlying genetic causes of this terrible disease, and this research brings us closer to realizing that end," Dr. Olson said.
"CRISPR-Cpf1 differs from CRISPR-Cas9 in a number of key ways, including being easier to deliver to muscle cells, said Yu Zhang, a graduate student in Dr. Olson's lab and the first author of this study.
Other UT Southwestern researchers who contributed to this work are Dr. Hui Li, research scientist; John R. McAnally, research scientist; Dr. Kedryn Baskin, postdoctoral researcher; and John M. Shelton, senior research scientist.
This work was supported by grants from the National Institutes of Health (NIH), a Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers grant, and a Robert A. Welch Foundation grant.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.
Cathy Frisinger | EurekAlert!
'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS
New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy