Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM).
Two germline retrotransposition mutations of recent origin were observed in 727 independent mutations (0.28%) in the human factor IX gene (F9) of patients with hemophilia B: 1) a 279 bp insertion in exon H originating from an Alu family of short interspersed elements not previously known to be active and, 2) a 463 bp insertion in exon E of a LINE1 element originating in the maternal grandmother.
For this study, determinants of FIX inhibitor development were compared in hemophilia B mice, in which circulating FIX protein is absent (CRM- factor IX knockout (FIXKO) model) or present (CRM+ missense R333Q-hFIX model) modeling multiple potential therapies.
Polymerase chain reaction analysis of DdeI/intron1, XmnI/intron 3 and HhaI/3' flanking region of the gene for factor IX (F9) was investigated in 68 individuals (23 haemophilia patients, 18 obligate carriers, 27 probable carriers) from 23 families of haemophilia B. Linkage disequilibrium analysis was done and haplotypes were generated employing the expectation-maximization algorithm.
T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.
52 kindreds, referred to as haemophilia B-, were characterized by severe deficiency of factor IX coagulant activity (less than 0.01--0.03 u/ml) and unmeasurable IX:Ag (less than 0.12 u/ml): this genetic variant of the disease appears to be related to a complete or marked suppression of factor IX synthesis.
We have reported the efficacy and safety of AMT-060, an investigational gene therapy comprising an adeno-associated virus serotype 5 capsid encapsidating the codon-optimized wild-type human factor IX (WT h<i>FIX</i>) gene with a liver-specific promoter, in patients with severe hemophilia B.
To generate sufficient clinical-grade vector to support a phase I/II clinical trial of adeno-associated virus serotype 8 (AAV8)-mediated factor IX (FIX) gene transfer for hemophilia B, we have developed a large-scale, good manufacturing practice (GMP)-compatible method for vector production and purification.
In this study, a more comprehensive analysis of the molecular pathology of haemophilia B in Turkey revealed one large deletion and 33 point mutations in the FIX gene of 34 unrelated patients.
Vector capsid dose-dependent inflammation of transduced liver has limited the ability of adeno-associated virus (AAV) factor IX (FIX) gene therapy vectors to reliably convert severe to mild hemophilia B in human clinical trials.
Recent data from a handful of patients who have undergone gene therapy for hemophilia B are very encouraging with a sustained factor IX (FIX) level of 0.05 IU/mL maintained for over 4 years.