"Hematology researchers have used a single injection of gene therapy to correct a rare bleeding disorder factor VII deficiency in dogs. This success in large animals holds considerable potential for a safe effective and longlasting new treatment in humans with the same bleeding disorder. Our finding has great clinical relevance for patients with factor VII deficiency said study leader Paris Margaritis D. Phil. a hematology researcher at the Raymond G. Perelman Center for Cellular and Molecular Therapeutics CCMT httpccmt.research.chop.edu at The Childrens Hospital of Philadelphia CHOP. These dogs have the type of mutation found in the majority of patients with this disorder so this approach could lead to a sustained gene therapy in people. The study appeared online Dec.  in Blood. The Margaritis team httpccmt.research.chop.edulabs_margaritis.php collaborated with University of North Carolina UNC scientists led by Tim Nichols M.D. professor of Medicine and Pathology at the UNC School of Medicine. Factor VII deficiency is rare found in about one in  to one in  people. Because a gene mutation impairs normal production of a blood clotting factor patients may suffer excessive bleeding in the central nervous system or GI tract or after surgery or an injury. Female patients may suffer excessive menstrual bleeding. Factor VII FVII deficiency has a range of severity with about  percent of patients having severe disease. They are most commonly treated with regular infusions of clotting factor. Unlike hemophilia a betterknown bleeding disorder that predominantly affects males factor VII deficiency strikes males and females equally. Gene therapy proposed for bleeding disorders involves introducing DNA carrying the code to produce the specific clotting factor lacking in patients. Researchers at CHOP and elsewhere have bioengineered an adenoassociated virus AAV which does not cause disease as a vector to deliver DNA into cells where it can express enough factor to make the blood clot normally. Over the past  years CHOP hematology researchers have performed clinical trials of gene therapy for hemophilia B that have helped define efficacy and dosing levels in humans. The CCMT at CHOP houses a clinicalgrade laboratory that manufactures gene therapy vectors including the AAV vectors used in the current study. Margaritis a member of the CHOP group long engaged in hemophilia research currently leads a laboratory focused on factor VII deficiency as well as hemophilia.  We developed a unique animal model of this disease after identifying dogs with naturally occurring factor VII deficiency said Margaritis. Our investigations enabled us to design the corrective gene to insert into our virus vector in the current study.  The CHOP team collaborated with scientists at UNC who have a longestablished colony of dogs for hematology research. Based on previous work by Margaritis the UNC team identified dogs for this gene therapy study.  Nichols the director of UNCs Francis Owens Blood Research Laboratory characterized factor VII deficiency in four individual dogs. Using the AAV vectors supplied by Margaritis Nichols injected the dogs with varying dosages and monitored their health outcomes and biological markers over several years.  The treated dogs had expressed levels of clotting factor VII that would be therapeutic in humans with longterm stability. In one dog the effects persisted nearly three years. Based on kidney function liver function and blood measurements in the dogs the treatment was safe and did not elicit unwanted immune responses. The current study sets the stage for clinical trials in humans. This gene therapy may especially benefit young children with severe bleeding from factor VII deficiency such as patients receiving care in CHOPs hematology program. This work is very exciting and promising said Nichols who added The FVIIdeficient dogs tolerated the initial gene therapy infusions very well and have had no adverse side effects over several years of follow up. In other related studies in dogs with hemophilia B similar positive findings have translated to people with hemophilia B. Both Nichols and Margaritis agreed The table is now set to propose clinical trials that would treat people who suffer from FVII deficiency.   The National Institutes of Health grants HL and HL the Howard Hughes Medical Institute and the Pennsylvania Department of Health supported this study. In addition to his CHOP position Margaritis is a faculty member at the Perelman School of Medicine at the University of Pennsylvania. Sustained correction of FVII deficiency in dogs using AAVmediated expression of zymogen FVII Blood published online Dec.  .  httpdoi.org.blood"