Researchers at UCLA from the Departments of Medicine and Urology have developed a treatment for hemophilia A that utilizes non-viral gene editing technologies for ex vivo repair of the mutation in the gene F8.
Hemophilia affects about 400,000 people worldwide, and approximately 80% of these cases are hemophilia A. Hemophilia A is an X-linked genetic disease caused by a mutation of the F8 gene. This mutation results in a deficiency of the blood coagulation protein factor VIII. Patients with the disease typically have spontaneous bleeding, as well as joint and muscle damage. These injuries can result in crippling arthropathy and physical disability. The current treatment for hemophilia involves the administration of clotting factors, either from a plasma infusion or recombinant protein production. Although these methods effectively manage hemophilia A, they are not curative. In addition, long-term treatment with recombinant proteins can cause immune responses due to contaminants from the source of purification. Plasma infusions possess risks associated with blood transfusions, such as viral transmission, alloimmunization, excessive intravascular volume, and acute lung injury. Ongoing efforts have attempted to use viral vectors, such as adeno-associated virus or lentivirus, to treat hemophilia patients. While there is great merit in these approaches, none has demonstrated efficacy for treating hemophilia A in humans. Both viral techniques have safety risks, including immunogenicity or incorporation into the genome, which results in dysregulation of normal cell differentiation. Thus, a safe and curative treatment for hemophilia A is greatly needed.
Researchers at UCLA from the Departments of Medicine and Urology have developed a treatment for hemophilia A that utilizes non-viral gene editing technologies, such as transcriptional activator-like effector nucleases (TALENs), zinc finger nucleases (ZFNs), and CRISPR-Cas, for ex vivo repair of the mutation in the gene F8. This autologous treatment is expected to restore a full length and functional Factor VIII and avoid the safety risks associated with viral-mediated gene repair.
The treatment method suggested by the inventor offers a novel, curative treatment for hemophilia A
This technology is at the conceptual phase. The inventors plan to perform several key in vivo experiments using canine animal models and ex vivo experiments in patient samples.
|United States Of America||Issued Patent||10,272,163||04/30/2019||2014-016|
|European Patent Office||Published Application||2928303||10/14/2015||2014-016|
Additional Patents Pending
Hemophilia A, gene editing, gene therapy, F8, Factor VIII, blood coagulation protein, transcriptional activator-like effector nucleases, TALEN, Zinc Finger Nucleases ZFN, CRISPR-Cas