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

Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Research Abstract Details 

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Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Abstract Text:

E F Cohn,J Zhuo,M E Kelly,H J Chao,

BACKGROUND: 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. OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Publishing Authors By Initials

EF Cohn,J Zhuo,ME Kelly,HJ Chao,

For similar biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research

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MEDLINE DATE:

Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of thrombosis and haemostasis : JTH

VOLUME: 5

Page Numbers: 1227-36

Journal Abbreviation: J. Thromb. Haemost.

ISSN: 1538-7933

DAY: 3

MONTH: Jun

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 101170508

Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Keywords Mesh Terms:

KEYWORDS: Species Specificity

MESH TERMS: immunology

Chemical & Substance for Abstract: Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer. Information

Substance Name: Factor IX

Registry Number: 9001-28-9

Grant and Affiliation Information for Efficient induction of immune tolerance to coagulation factor IX following direct intramuscular gene transfer.

AFFILIATION: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

Country: England

AGENCY: United States NHLBI

GRANT: R01-HL076699

ACRONYM: HL

MEDLINETA: J Thromb Haemost

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