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    CRISPR/Cas9 therapeutic for tyrosinemai type I delivered to mice

    University of Massachusetts Medical School researchers have now developed a way to deliver the CRISPR genome repair components more efficiently than previously possible, and they also believe it may be safer for human use.
    A study published in Nature Biotechnology on Feb. 1st shows that administering the treatment by combining two delivery mechanisms already in clinical trials for other diseases led to correction of the mutated gene that causes the rare liver disorder in 6 percent of liver cells -- enough to effectively cure the disease in mice.
    Type 1 Tyrosinemia, also known as hepatorenal tyrosinemia, is caused by the inability to metabolize the amino acid tyrosine. It is caused by a mutation in the FAH gene, which codes for the enzyme fumarylacetoacetate hydrolase. This leads to a toxic build-up of metabolites in the blood and urine, causing severe damage to the liver and kidneys.
    Researchers loaded a CRISPR guide RNA and the genetic repair template into a reprogrammed AAV vector and injected it into mice. Because these genetic materials are being delivered with a viral vector, they can be expressed over a prolonged period of time, alleviating the need to deliver them simultaneously with Cas9. Without the Cas9 messenger RNA to cut the genome, the CRISPR guide and repair template remain inactive in the cells. A week later, after the liver cells have had time to begin producing the RNA guide strand and the DNA template, a lipid nanoparticle is used to deliver the Cas9 messenger RNA.
    "This is the first study to provide proof that the CRISPR/Cas9 gene editing system can be administered in a therapeutically applicable formulation to repair genes in live, adult animals," said Wen Xue, PhD, assistant professor of molecular medicine and a member of the RNA Therapeutics Institute at UMass Medical School.
    Read more: Hao Yin et. al “Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo”, Nature Biotechnology. doi:10.1038/nbt.3471