75 YEARS OF VISION: THE LASTING GIFT
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s biomedical research continued to identify genetic mutations that lead to disease, a
revolutionary genome editing tool called CRISPR was discovered. Jennifer Doudna of the University of California, Berkeley, and Emmanuelle Charpentier of Umeå University, Sweden, won a 2015 Breakthrough Prize in Life Sciences for “harnessing an ancient mechanism of bacterial immunity into a powerful and general technology for editing genomes.” In the 1980s, scientists had observed an odd pattern in bacterial genomes where a DNA sequence would repeat over and over again with unique sequences appearing between the repeats. The configuration was called “clustered regularly interspaced short palindromic repeats,” or CRISPR. Decades later, researchers realized the sequences matched the DNA of viruses that
CRISPR was used to splice DNA from an extinct woolly mammoth into that of an elephant. Scientists were then able to use the “revived” DNA to sequence the mammoth’s approximate genome.
prey on bacteria. CRISPR was, in fact, a naturally occurring tool of the bacteria’s immune system that stores sections of dangerous viruses so it can recognize and defend against them the next time they attack. A second tool was identified: a set of enzymes called Cas (CRISPR-associated
proteins), which snips the invading DNA; the best known was called Cas9. Working together, Cas9 snips sections of DNA, and CRISPR tells Cas9 precisely where to snip. GENE EDITING
OLSON
THE LARGEST human gene, DMD, provides the instructions for making a protein called dystrophin. A mutation in the DMD gene can cause Duchenne Muscular Dystrophy, a fatal genetic disorder characterized by muscle degeneration and weakness. Genes occur in sections called exons. The DMD gene has 79 such exons but can retain its function even if a few in the middle are removed. A strain of laboratory mice was developed in which dystrophin production failed because of a mutation in the 23rd DMD exon.
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In 2015, UT Southwestern researchers led by Eric Olson, PhD, used CRISPR/Cas9 to stop the progression of Duchenne Muscular Dystrophy in young mice. Researchers loaded the gene-editing system and the identifying guides into a harmless virus that swept through the bodies of the mice, cutting the two ends of the 23rd exon and removing the damaged exon. As a result, the gene was able to produce functioning dystrophin proteins. Their incredible discovery could lead to the first successful genome editing-based treatment of DMD in humans. With the opportunity of such genetic editing comes enormous responsibility, opening up a vast new world of risks and rewards, as well as moral and ethical questions. In December, an international group of scientists met in Washington and agreed that experimenting with human embryos destined to develop into children would, for the foreseeable future, be “irresponsible.” But
the scientists endorsed exploring gene editing as a medical treatment – altering the genes of immune cells to make them capable of killing cancer, for example. “To launch a clinical trial, we need to scale up, improve efficiency and assess safety,” Dr. Olson said. “I think within a few years those issues can be addressed.” On December 23, the National Institutes of Health awarded UT Southwestern Medical Center researchers a $7.8 million grant to establish a Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center – one of six nationally – to further research for new treatments using the gene editing technique. Dr. Olson co-directs the Wellstone Muscular Dystrophy Center with Dr. Pradeep Mammen, Associate Professor of Internal Medicine and Medical Director of UT Southwestern’s Neuromuscular Cardiomyopathy Clinic.
ifts to the Foundation and Medical Center have, over the decades, established hundreds
of centers, chairs, professorships and scholarships in support of medical research and clinical care. One of countless examples occurred in May, when the Hersh Foundation gave a $5 million lead gift to the Foundation to help establish the Center for Depression Research and Clinical Care and to endow the Julie K. Hersh Chair in Depression Research and Clinical Care. Julie K. Hersh
“Julie has been one of the most informed and active members of the Board of Southwestern Medical Foundation,” said Kathleen Gibson, Foundation President. “This important gift and Julie’s passionate work in helping to advance the science and treatment of mood disorders are the epitome of active community leadership.”
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