Tag Archives: CRISPR-Cas9

How To Treat Congenital Disease Before Birth

For the first time, scientists have performed prenatal gene editing to prevent a lethal metabolic disorder in laboratory animals, offering the potential to treat human congenital diseases before birth. Published today in Nature Medicine, research from the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) and offers proof-of-concept for prenatal use of a sophisticated, low-toxicity tool that efficiently edits DNA building blocks in disease-causing genes.

Using both CRISPR-Cas9 and base editor 3 (BE3) gene-editing tools, the team reduced cholesterol levels in healthy mice treated in utero by targeting a gene that regulates those levels. They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice that had been engineered with a mutation causing the lethal liver disease hereditary HT1 (HT1). HT1 in humans usually appears during infancy, and it is often treatable with a medicine called nitisinone and a strict diet. However, when treatments fail, patients are at risk of liver failure or liver cancer. Prenatal treatment could open a door to disease prevention, for HT1 and potentially for other congenital disorders.

Our ultimate goal is to translate the approach used in these proof-of-concept studies to treat severe diseases diagnosed early in pregnancy,” said study co-leader William H. Peranteau, MD, a pediatric and fetal surgeon in CHOP’s Center for Fetal Diagnosis and Treatment. “We hope to broaden this strategy to intervene prenatally in congenital diseases that currently have no effective treatment for most patients, and result in death or severe complications in infants.

We used base editing to turn off the effects of a disease-causing genetic mutation,” said study co-leader Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. “We also plan to use the same base-editing technique not just to disrupt a mutation’s effects, but to directly correct the mutation.” Musunuru is an expert in gene-editing technology and previously showed that it can be used to reduce cholesterol and fat levels in the blood, which could lead to the development of a “vaccination” to prevent cardiovascular disease.

Source: https://www.pennmedicine.org/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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CRISPR Reverses Duchenne Muscular Dystrophy Mutation

CRISPR-Cas9 has, for the first time, been tested by systemic delivery in a large animal—and the results are striking. Working in a dog model of Duchenne muscular dystrophy (DMD), the gene editing not only restored the expression of the protein dystrophin, it also improved muscle histology in the dogs.

Our technology was developed using human cells and mice to correct the same type of mutation as in these dogs. It was critical for us to test gene editing in a large animal because it harbors a mutation analogous to the most common mutation in DMD patients,” said Eric Olson, Ph.D., professor and chair of molecular biology at the University of Texas Southwestern Medical Center and lead author. The researchers wrote that this is “an essential step toward clinical translation of gene editing as a therapeutic strategy for DMD.”

Indeed, Dame Kay E. Davies, Ph.D., professor of anatomy and director of the MRC Functional Genomics Unit at the University of Oxford and a pioneer in the field of DMD research, echoes this sentiment explains, “This is a very exciting paper as it shows that gene editing can be reasonably affective in a large animal model of DMD.”

The paper, “Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy,” appears in the last issue of Science.

Source: https://www.genengnews.com/