Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies
نویسندگان
چکیده
منابع مشابه
Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies
Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor IX (FIX) are difficult to eradicate due to anaphylactic reactions and nephrot...
متن کاملLiver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice
A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to ...
متن کاملFactor IX variants improve gene therapy efficacy for hemophilia B.
Intramuscular injection of adeno-associated viral (AAV) vector to skeletal muscle of humans with hemophilia B is safe, but higher doses are required to achieve therapeutic factor IX (F.IX) levels. The efficacy of this approach is hampered by the retention of F.IX in muscle extracellular spaces and by the limiting capacity of muscle to synthesize fully active F.IX at high expression rates. To ov...
متن کاملPathogenic antibodies to coagulation factors. Part one: factor VIII and factor IX.
Pathogenic antibodies targeting coagulation factors usually are clinically significant because they inhibit function. Circulating anticoagulants were recognized as early as 1906 ([1], cited in [2]). They interfere with the coagulation of normal blood as well as that of the patient, which is the basis of the classical mixing study. Circulating anticoagulants inhibiting factor (F)VIII and factor ...
متن کاملGENE THERAPY Factor IX variants improve gene therapy efficacy for hemophilia B
Intramuscular injection of adeno-associated viral (AAV) vector to skeletal muscle of humans with hemophilia B is safe, but higher doses are required to achieve therapeutic factor IX (F.IX) levels. The efficacy of this approach is hampered by the retention of F.IX in muscle extracellular spaces and by the limiting capacity of muscle to synthesize fully active F.IX at high expression rates. To ov...
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ژورنال
عنوان ژورنال: EMBO Molecular Medicine
سال: 2013
ISSN: 1757-4676,1757-4684
DOI: 10.1002/emmm.201302859