Vector constructs The codon-optimized human FIX cDNA (co-hFIX) or its hyper-functional codon-optimized version (co-hFIX-R338L) were cloned downstream of a chimeric liver-specific promoter composed on the minimal transthyretin (TTR) promoter in combination with a hepatocyte-specific cis-regulatory module (designated as HS-CRM8) that was designed in silico, as described 1,2. This HS-CRM8 contains...

A potentially cost-effective strategy for gene therapy of hemophilia B is to create universal factor IX-secreting cell lines suitable for implantation into different patients. To avoid graft rejection, the implanted cells are enclosed in alginate-polylysine-alginate microcapsules that are permeable to factor IX diffusion, but impermeable to the hosts' immune mediators. This nonautologous approa...

Coagulation factor IX is a vitamin K-dependent glycoprotein that circulates in blood as a precursor of a serine protease. Incubation of human factor IX with human alpha-thrombin resulted in a time and enzyme concentration-dependent cleavage of factor IX yielding a molecule composed of a heavy chain (mol wt 50,000) and a doublet light chain (mol wt 10,000). The proteolysis of factor IX by thromb...

only DESCRIPTION Coagulation Factor IX (Human), Mononine, is a sterile, stable, lyophilized concentrate of Factor IX prepared from pooled human plasma and is intended for use in therapy of Factor IX deficiency, known as Hemophilia B or Christmas disease. Mononine is purified of extraneous plasma-derived proteins, including Factors II, VII and X, by use of immunoaffinity chromatography. A murine...

Recombinant adeno-associated virus (AAV) vectors show promise for use in gene therapy. For liver-targeted gene transfer in animals, AAV vectors pseudotyped with the AAV serotype 8 (AAV8) capsid have definite advantages over the widely used but less efficient serotype AAV2, even though the capsid amino acid sequences are 82% conserved. To demonstrate the mechanism behind the higher liver transdu...

background: heterogeneous mutations in the human coagulation factor ix gene lead to an x-linked recessive bleeding disorder known as hemophilia b. the disease is distributed worldwide with no ethnic or geographical priority. materials and methods: the aim of this study was to characterize the factor ix gene mutations in 28 unrelated iranian hemophilia b patients. polymerase chain reaction (pcr)...

Background: Hemophilia B is a bleeding disorder with a recessive X-linked inheritance pattern, in which the infected individuals have low levels of factor IX in their plasma. Affected individuals may have bleeding episodes after trauma or spontaneously considering the plasma level of factor IX. In order to prevent these episodes and to control bleeding, they should use coagulation factor concen...

Our laboratory develops protocols to prevent or reverse ongoing anti-hFIX IgG inhibitors in haemophilia B mice with a F9 gene deletion on BALB/c and C3H/HeJ backgrounds. C3H/HeJ F9(-/Y) mice develop high titre anti-hFIX IgG1 inhibitors and anaphylaxis, whereas most BALB/c F9(-/Y) mice have mild anti-hFIX IgG1 inhibitors and no anaphylaxis. Our aim was to determine if hFIX-specific B- and T-cell...

Immunoaffinity chromatography using conformation-specific antibodies yields pure factor IX from human plasma in a single rapid, facile purification step. We evaluated this technique to determine whether factor IX can be separated from human T cell leukemia virus-I (HTLV-I) and human immunodeficiency virus (HIV) in plasma supplemented with these viruses. Viral content was determined with an enzy...

Understanding host responses to viral gene therapy vectors is necessary for the development of safe and efficacious in vivo gene transfer agents. We describe the use of high-density spotted complementary DNA microarrays in monitoring the in vivo host transcriptional responses in mouse liver upon administration of either a "first-generation"adenoviral (Ad) vector, a helper-dependent "gutless" ad...