NDLI: Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer

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Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer

Content Provider	Scilit
Author	Cohn, E. F. Zhuo, J. Kelly, M. E. Chao, H. J.
Copyright Year	2007
Description	Journal: Journal of Thrombosis and Haemostasis The formation of inhibitory anti-factor IX (anti-FIX) antibodies is a major complication of FIX protein replacement-based treatment for hemophilia B. It is difficult to treat patients with anti-FIX antibodies. Gene therapy is emerging as a potentially effective treatment for hemophilia. Direct i.m. injection of adeno-associated virus (AAV) is a safe and efficient procedure for hemophilia B gene therapy. However, the development of anti-FIX antibodies following i.m. of AAV may impede its application to patients. We aimed to investigate induction of immune tolerance to human FIX (hFIX) by i.m. of AAV1, further validating i.m. of AAV1 for hemophilia B gene therapy. Cohorts of hemostatically normal and hemophilia B mice with diverse genetic and MHC backgrounds received i.m. of AAV-hFIX. Human FIX antigen and anti-hFIX antibodies were examined. I.m. of 1 x 10(11) vector genomes (VG) of AAV2 elicits formation of anti-hFIX antibodies comparable to those by hFIX protein replacement. I.m. of 1 x 10(11) VG of AAV1 results in expression of therapeutic levels of hFIX (up to 950 ng mL(-1), mean = 772 ng mL(-1), SEM +/- 35.7) and hFIX-specific immune tolerance in C57BL/6 mice. A single i.m. of AAV1 can result in efficient expression of therapeutic levels of hFIX and induction of hFIX tolerance in hemostatically normal and hemophilic B mice. Our results substantiate the prospect of i.m. of AAV1 for hemophilia B gene therapy and FIX tolerance induction.
Ending Page	1236
Starting Page	1227
ISSN	2573508X
e-ISSN	15387836
DOI	10.1111/j.1538-7836.2007.02522.x
Journal	Journal of Thrombosis and Haemostasis
Issue Number	6
Volume Number	5
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2007-06-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Thrombosis and Haemostasis Biochemistry and Molecular Biology Adeno‐associated Virus Factor Ix Gene Therapy Hemophilia B Immune Tolerance
Content Type	Text
Resource Type	Article

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