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Gene therapy, bioengineered clotting factors and novel technologies for hemophilia treatment
Author(s) -
PIERCE G. F.,
LILLICRAP D.,
PIPE S. W.,
VANDENDRIESSCHE T.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02410.x
Subject(s) - genetic enhancement , clotting factor , medicine , clinical trial , factor ix , ex vivo , viral vector , gene delivery , gene transfer , immunology , immune system , vector (molecular biology) , in vivo , intensive care medicine , bioinformatics , pharmacology , gene , biology , recombinant dna , microbiology and biotechnology , genetics
Summary. The World Federation of Hemophilia estimates that of the 400 000 individuals worldwide with hemophilia, 300 000 receive either no, or very sporadic, treatment. Thus, considerable innovation will be required to provide cost‐effective therapies/cures for all affected individuals. The high cost of prophylactic regimens hampers their widespread use, which further justifies the search for novel cost‐effective therapies and ultimately a cure. Five gene transfer phase I clinical trials have been conducted using either direct in vivo gene delivery with viral vectors or ex vivo plasmid transfections and reimplantation of gene‐engineered cells. Although there was evidence of gene transfer and therapeutic effects in some of these trials, stable expression of therapeutic factor VIII or FIX levels has not yet been obtained. Further improvements of the vectors and a better understanding of the immune consequences of gene transfer is warranted, as new trials are being initiated. Bioengineered clotting factors with increased stability and/or activity are being validated further in preclinical studies. Novel clotting factor formulations based on PEGylated liposomes with prolonged activities are being tested in the clinic, and are yielding encouraging results.