TIME Health Heart Disease  
    Doctors, and especially doctors who do research, dont like to    use the words cure or eradicate. They know how dangerous that    can be, since the human body is so unpredictable. But Dr. Kiran    Musunuru is showing some uncharacteristic swagger about his    latest success in lowering heart attack risk among some lucky    mice.  
    Taking advantage of advances in genetic engineering, a team    lead by Musunuru, who holds positions at Harvard Universitys    Department of Stem Cell and Regenerative Biology and Brigham    and Womens Hospital, have edited the genomes of mice and    successfully protected them from heart disease. The results,    published in the journal Circulation Research, hint at    an entirely new way of avoiding the leading killer of Americans    by possibly cutting heart attack risk by up to 90%. What has    me excited as a cardiologist is that my goal is eradicating    disease, says Musunuru. There is no bolder way I can put it.    I want to eradicate the disease and this offers one potential    way to do it.  
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    He admits that it may be 10 years or more before the technique    is ready for testing in people, but these first results are    enough to justify the research that could make that happen.    This approach in general will be a game changer, says Dr.    Deepak Srivastava, director of cardiovascular disease and stem    cell biology and regenerative medicine at the Gladstone    Institutes, who was not affiliated with the study.  
    Heres how they did it. In 2003, genetic information was    gleaned from a French family that carried a genetic mutation    giving them low LDL cholesterol, the kind that, when its high,    can lead to heart disease. Using a new genetic engineering    technique that allows scientists to splice more efficiently    into specific locations on a genome, Musunuru was able to    essentially bestow the genetic advantage from the French family    onto his mice, slowing down production of a protein that    normally keeps LDL circulating in the blood. With less of the    protein around, less LDL remains in the blood; those with the    PCSK9 mutation showed as much as an 88% lower risk of heart    disease compared to people without the genetic change.  
    The genetic monkeying was accomplished with the help of a    virus, which has a remarkable ability to get into cells. The    virus was injected, along with the DNA-disrupting machinery,    into the liver of the mice. Within days, more than half of the    liver cells had been genetically edited and the mice showed 35%    to 40% less cholesterol in the blood.  
    So far, says Musunuru, there have been no negative effects of    the genetic disruption. But he says more research needs to be    done to make sure that introducing the changes wont come with    unforeseen consequences. When we go in there we want to make    sure we are not introducing new spelling errors in the genome,    says Srivastava, who is also using the technique for stem-cell    based therapies to treat heart disease. Says Musunuru, I think    I can confidently say that with this tool, this technology will    work on live, breathing human beings, but we need to figure out    the safety; thats the barrier to overcome before we can test    these therapies.  
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    Drug companies are also working on drug-based ways to interfere    with PCSK9, and lower LDL levels, but those therapies are    antibodies that bind to the protein that the gene makes and    need to be injected, at a doctors office, regularly. The    genome editing strategy would be a one-stop therapy that could    permanently protect against excessively high cholesterol    levels.  
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