Nav: Home

Gene-editing alternative corrects Duchenne muscular dystrophy

April 12, 2017

DALLAS - April 12, 2017 - 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.

"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.

It also recognizes a different sequence of DNA than Cas9 does, which provides greater flexibility in terms of use. "There will be some genes that may be difficult to edit with Cas9 but may be easier to modify with Cpf1, or vice versa. The two proteins have different biochemical properties and recognize different DNA sequences, so these properties create more options for gene-editing," said Dr. Olson, who holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research.

For more information:

"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.
-end-
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.
-end-
This news release is available on our website at http://www.utsouthwestern.edu/news.

To automatically receive news releases from UT Southwestern via email, subscribe at http://www.utsouthwestern.edu/receivenews

UT Southwestern Medical Center

Related Molecular Biology Articles:

Cell biology: Your number's up!
mRNAs program the synthesis of proteins in cells, and their functional lifetimes are dynamically regulated.
Cell biology: All in a flash!
Scientists of Ludwig-Maximilians-Universitaet (LMU) in Munich have developed a tool to eliminate essential proteins from cells with a flash of light.
A biology boost
Assistance during the first years of a biology major leads to higher retention of first-generation students.
Scientists find biology's optimal 'molecular alphabet' may be preordained
Life uses 20 coded amino acids (CAAs) to construct proteins.
Molecular biology: Phaser neatly arranges nucleosomes
LMU researchers have, for the first time, systematically determined the positioning of the packing units of the fruit fly genome, and discovered a new protein that defines their relationship to the DNA sequence.
Molecular virologist fights influenza at the molecular level
In research to improve influenza therapies against H7N9 and other influenza strains, Chad Petit and his University of Alabama at Birmingham colleagues have detailed the binding site and mechanism of inhibition for two small-molecule experimental inhibitors of influenza viruses.
The complicated biology of garlic
Researchers generally agree that garlic, used for thousands of years to treat human disease, can reduce the risk of developing certain kinds of cancers, cardiovascular disease, and type 2 diabetes.
Study suggests molecular imaging strategy for determining molecular classifications of NSCLC
Recent findings suggest a novel positron emission tomography (PET) imaging approach determining epidermal growth factor receptor (EGFR) mutation status for improved lung cancer patient management.
The biology of color
Scientists are on a threshold of a new era of color science with regard to animals, according to a comprehensive review of the field by a multidisciplinary team of researchers led by professor Tim Caro at UC Davis.
Molecular microscopy illuminates molecular motor motion
A toddler running sometimes loses footing because both feet come off the ground at the same time.
More Molecular Biology News and Molecular Biology Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.