Sangamo BioSciences Announces Publication of First Demonstration of In Vivo Correction of Hemophilia Gene via Systemic Delivery of a ZFP Therapeutic®

Sangamo BioSciences, Inc. announced today the publication of a groundbreaking preclinical study demonstrating permanent functional correction of the gene that causes hemophilia B by the systemic delivery of zinc finger nucleases (ZFNs) . The study, published in Nature, represents a significant advance in the development and systemic delivery of ZFP Therapeutics® and proof of concept for ZFN-based gene-editing for the treatment of hemophilia and other monogenic diseases.
The work was carried out in the laboratory of Katherine High, M.D., Investigator, Howard Hughes Medical Institute, Professor of Pediatrics, University of Pennsylvania School of Medicine and Director, Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, in collaboration with Sangamo scientists and was published as an Advance Online Publication in Nature.

"These data represent a significant advance in realizing efficient, systemic, therapeutic gene repair - the 'holy grail' of genetic medicine," said Dr. High, "With a single systemic administration of ZFNs and a donor sequence in a mouse model of hemophilia B, we demonstrated permanent correction of a defective human gene encoding the clotting factor, Factor IX, resulting in restoration of normal clotting times in the animal. ZFN-mediated gene-editing provides a new approach to monogenic disease and circumvents the problems of traditional gene-addition strategies that result in random insertion that may lead to malignancy or other unintended consequences. Genome editing also reinstates the wild-type sequence under the control of the endogenous regulatory sequences, assuring restoration of this critical aspect of normal gene expression. The study also demonstrated that permanent correction of the disease-related gene in situ can be achieved with therapeutically meaningful correction efficiencies."

"This is an important step forward in our goal to broaden the application of ZFN gene-editing via in vivo administration," stated Edward Lanphier, Sangamo's president and chief executive officer. "These data highlight the therapeutic potential of our ZFN technology and enable us to expand our ZFP Therapeutic pipeline to a growing number of monogenic and rare diseases."

The paper entitled "In vivo Genome Editing Restores Hemostasis in a Mouse Model of Hemophilia" described highly specific and efficient ZFN-mediated correction of a defective human Factor IX gene in a mouse model of hemophilia B by the delivery of ZFNs directly into animals. Stable levels of Factor IX protein made from the corrected human gene were measured in the plasma of the treated animals and resulted in the restoration of normal rates of blood clotting for the eight-month duration of the study. Moreover, the treatment was well tolerated as there were no deleterious effects on growth or liver function in the animals.