Using an innovative gene therapy technique called genome editing that hones in on the precise location of mutated DNA, scientists have treated the blood clotting disorder hemophilia in mice. This is the first time that genome editing, which precisely targets and repairs a genetic defect, has been done in a living animal and achieved clinically meaningful results.
As such, it represents an important step forward in the decades-long scientific progression of gene therapydeveloping treatments by correcting a disease-causing DNA sequence. In this new study, researchers used two versions of a genetically engineered virus (adeno-associated virus, or AAV)one carrying enzymes that cut DNA in an exact spot and one carrying a replacement gene to be copied into the DNA sequence. All of this occurred in the liver cells of living mice.
"Our research raises the possibility that genome editing can correct a genetic defect at a clinically meaningful level after in vivo delivery of the zinc finger nucleases," said the study leader, Katherine A. High, M.D., a hematologist and gene therapy expert at The Children's Hospital of Philadelphia. High, a Howard Hughes Medical Institute Investigator, directs the Center for Cellular and Molecular Therapeutics at Children's Hospital, and has investigated gene therapy for hemophilia for more than a decade.
The study appeared online today in Nature.
High's research, a collaboration with scientists at Sangamo BioSciences, Inc., makes use of genetically engineered enzymes called zinc finger nucleases (ZFNs) that act as molecular word processors, editing mutated sequences of DNA. Scientists have learned how to design ZFNs custom-matched to a specific gene location. ZFNs specific for the factor 9 gene (F9) were designed and used in conjunction with a DNA sequence that restored normal gene function lost in hemophilia.
By precisely targeting a specific site along a chromosome, ZFNs have an
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Children's Hospital of Philadelphia