Published in Human Gene Therapy
Adeno-associated virus (AAV)-U7-mediated skipping of dystrophin-exon-23 restores dystrophin expression and muscle function in the mdx mouse model of Duchenne muscular dystrophy. Soluble activin receptor IIB (sActRIIB-Fc) inhibits signaling of myostatin and homologous molecules and increases muscle mass and function of wild-type and mdx mice. We hyp...
Published in Human Gene Therapy
Mao and colleagues demonstrate that a single injection of an adeno-associated viral vector based on rhesus serotype 10 into the vitreous is capable of expressing an anti-vascular endothelial growth factor antibody in the eye and suppressing retinal neovascularization.
Published in Human Gene Therapy
Flotte and colleagues report on a phase 2 trial in which the same α1-antitrypsin (AAT) AAV vector as in phase 1 is administered intramuscularly to nine AAT-deficient individuals at one of three doses. Vector-derived expression of normal (M-type) AAT in serum is shown to be dose dependent, peaks on day 30, and persists for at least 90 days, although...
Published in Human Gene Therapy
Zinc-finger nucleases (ZFNs) are artificial nucleases that can be designed to specifically cleave DNA at a chosen target gene. In this review article, Rahman and colleagues describe how ZFNs have been applied to models of gene therapy, discuss the opportunities and risks associated with this novel technology, and suggest future directions for their...
Published in Human Gene Therapy
Watts and colleagues compare the effects of HOXB4 and NUP98-HOXA10hd on the expansion and engraftment of CD34+ cells. A competitive repopulation assay using CD34+ cells modified with gammaretroviral vectors expressing HOXB4YFP or NA10hdGFP was performed in pigtailed macaques. HOXB4YFP contributed more to early hematopoiesis whereas NA10hdGFP had a ...
Published in Human Gene Therapy
Zhang and colleagues examine the efficacy of a replication-competent parainfluenza virus (PIV)-based vector for airway gene transfer applications. Using an in vitro model of rhesus airway epithelium, the authors demonstrate that PIV mediates efficient gene transfer in rhesus epithelium. In vivo experiments revealed that intranasal administration of...
Published in Human Gene Therapy
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal childhood neurodegenerative lysosomal storage disease with no known therapy. There are estimated to be 200 to 300 children in the United States at any one time with the disease. LINCL is a genetic disease resulting from a deficiency of tripeptidyl peptidase I (TPP-I), a proteolytic en...
Published in Human Gene Therapy
Extracellular matrix dysregulation is key to the development of pulmonary hypertension (PH), suggesting a pivotal role for the proteases that control matrix remodeling. Both hypoxia- and monocrotaline-induced PH are associated with increased protease activity in the distal and proximal pulmonary arteries. However, the role of proteases is not compl...
Published in Human Gene Therapy
Gene therapy may provide a long-term approach to the treatment of mucopolysaccharidoses. As a first step toward the development of an effective gene therapy for mucopolysaccharidosis type IVA (Morquio syndrome), a recombinant retroviral vector, LGSN, derived from the LXSN vector, containing a full-length human wildtype N-acetylgalactosamine-6-sulfa...
Published in Human Gene Therapy
Gene therapy may provide a long-term approach to the treatment of mucopolysaccharidoses. As a first step toward the development of an effective gene therapy for mucopolysaccharidosis type IVA (Morquio syndrome), a recombinant retroviral vector, LGSN, derived from the LXSN vector, containing a full-length human wildtype N-acetylgalactosamine-6-sulfa...
