The sheep is a well-recognized model for studies on human fetal physiology and respiratory physiology. More recently, we have extended our in utero gene therapy approach to the sheep fetus. Although this has been reproduced with different batches of virus preparations, we found that the degree and intensity of transgene expression varied considerably even between fetuses of the same litter indicating that intake of the virus is not the only factor influencing airway infection (Buckley, in preparation). 6 We have been able to achieve adenovirus transduction of the airways in about 90% of our fetally treated mice. Our investigations in mice have shown that it is possible to achieve high level of widespread gene delivery to the fetal airways after intra-amniotic adenovirus application from day 15 of gestation onwards. 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 However, it has proven remarkably difficult to achieve consistent gene transfer to the airway epithelia in utero, which could be considered as sufficient to validate this procedure as a model for future in utero gene therapy of CF. 1 Several groups have therefore attempted to achieve transfer of marker genes to the fetal airways in rodents, sheep and primates.
Owing of its early onset and unsatisfactory prognosis, cystic fibrosis (CF) has been one of the first diseases to be considered for fetal gene therapy aiming to achieve a more effective transduction of the airway epithelia, avoid immune sensitization against vector and transgene, and prevent early-onset tissue damage. Using a percutaneous ultrasound-guided injection technique, we have clearly demonstrated proof of principle for substantial transgene delivery to the fetal airways providing levels of gene expression that could be relevant for a therapeutic application of CFTR expressing vectors. However, complexation of the virus with DEAE dextran, which confers a positive charge to the virus, and pretreatment of the airways with Na-caprate, which opens tight junctions, increased transgene expression, and a combination of these two enhancers resulted in widespread and efficient gene transfer of the fetal trachea and bronchial tree. Injection of adenoviral particles to the fetal airways was not associated with mortality and resulted in low-level expression in the peripheral airways. We report here on the delivery of a β-galactosidase expressing adenovirus directly to the airways of fetal sheep in utero using ultrasound-guided percutaneous injection of the trachea in the fetal chest. Although a candidate disease for in utero gene therapy, demonstration of potentially therapeutic levels of transgene expression in the fetal airways after minimally invasive gene delivery is a mandatory prerequisite before application of this approach in humans can be considered. There are a few extra utilities (weather forecast, yellow page search.Cystic fibrosis is a common lethal genetic disease caused by functional absence of the cystic fibrosis transmembrane conductance regulator (CFTR).
This is a great free GPS app with voice commands and recalculating capabilities. Routing works really well and accurate. GPS positioning is fast (faster than BB maps or Google maps) Arrow view loads quicker and consumes less of your dataplan You can choose between map view and arrow view. Maps load a bit slow on GPRS because they are very detailed. Next you encounter a 8800 bug, it says to hit the P-key to start, but it's actually the O-key (they brought it over from the Pearl incorrectly, it's still beta for the 8800) When you first launch the app you need to login or create a new user (this is best done from the site, it's free)Ĥ.
Downloaded the app to my pc and installed it without problems using the apploader.ģ.
OTA download from their site didn't work out (error 500).Ģ. I just installed amAze GPS ( ) on my 8800.ġ.