Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice.

Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero-injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR.

Assessment of endostatin gene therapy for familial adenomatous polyposis-related desmoid tumors.

Constitutive activation of the Wnt signaling pathway is a hallmark of many cancers, including familial adenomatous polyposis (FAP)-related desmoid tumors. Endostatin is a well-known antiangiogenic protein that has been described recently as a potential inhibitor of this signaling pathway. Here, we show that endostatin directly induces apoptosis and inhibits the Wnt signaling pathway in colorectal cancer cell lines bearing mutations on the adenomatous polyposis coli (APC) gene as a model of FAP-related malignant cells.

Bacterial gene therapy strategies.

The ability of bacteria to mediate gene transfer has only recently been established and these observations have led to the utilization of various bacterial strains in gene therapy. The types of bacteria used include attenuated strains of Salmonella, Shigella, Listeria, and Yersinia, as well as non-pathogenic Escherichia coli. For some of these vectors, the mechanism of DNA transfer from the bacteria to the mammalian cell is not yet fully understood but their potential to deliver therapeutic molecules has been demonstrated in vitro and in vivo in experimental models.

Factors influencing adenovirus-mediated airway transduction in fetal mice.

Intra-amniotic injection of adenovirus allows transduction of the fetal airways following natural fetal breathing movements. This administration method is promising for use in gene therapy for cystic fibrosis and other diseases for which the main target for exogenous gene expression is the lung. Here we have investigated factors that may affect the efficacy of gene transfer to the murine fetal lung.

Direct comparison of the insulating properties of two genetic elements in an adenoviral vector containing two different expression cassettes.

Targeted gene expression can be achieved through the use of cell-selective promoters. However, when the expression cassette is delivered by an adenovirus, "promoter interference," resulting in the loss of specificity, has been reported. To overcome this problem, insulator elements (the bovine growth hormone transcription stop signal or HS4 chromatin insulators of the chicken beta-globin locus) have been used.