The successful application of gene therapy for the treatment of genetic diseases such as Fabry is reliant on the development of vectors that are safe and that facilitate sustained expression of therapeutic levels of the transgene product. Here, we report that intravenous administration of a recombinant AAV2 vector encoding human alpha-galactosidase A under the transcriptional control of a liver-restricted enhancer/promoter (AAV2/DC190-alphagal) generated significantly higher levels of expression in BALB/c and Fabry mice than could be realized using the ubiquitous CMV promoter (AAV2/CMVHI-alphagal). Moreover, AAV2/DC190-alphagal-mediated hepatic expression of alpha-galactosidase A was sustained for 12 months in BALB/c mice and was associated with a significantly reduced immune response to the expressed enzyme. Subsequent challenge of the AAV2/DC190-alphagal-treated animals with recombinant human alpha-galactosidase A at 6 months failed to elicit the production of anti-alpha-galactosidase A antibodies, suggesting the induction of immune tolerance in these animals. The levels of expression attained with AAV2/DC190-alphagal in the Fabry mice were sufficient to reduce the abnormal accumulation of globotriaosylceramide in the liver, spleen, and heart to basal levels and in the kidney by approximately 40% at 8 weeks. Together, these results demonstrate that AAV2-mediated gene transfer that limits the expression of alpha-galactosidase A to the liver may be a viable strategy for treating Fabry disease.

The purpose of this study was to determine the effectiveness of the Water Pik oral irrigator as a vehicle for delivering an aqueous solution into periodontal pockets. Plaque-disclosing dye diluted with sterile saline solution was applied with the irrigator toward the gingival margins of teeth at 90 degrees and at 45 degrees prior to their extraction. The mean % penetration measured between a reference notch at the gingival crest and the periodontal ligament at the bottom of the pocket showed no statistical difference between the two angles of application. Penetration ranged from 44% to 71%, the lowest being into pockets 4-7 mm; higher mean penetration was noted in both subgroups 0-3 and greater than 7 mm. No statistical difference was found between proximal and facial or lingual surfaces, maxilla and mandible, existence of tooth contact, and proximal tissue contour or consistency. The mean % penetration was independent of pocket depth (chi 2 analysis). Correlation between pocket depth and mean penetration was low for all but one subgroup (90 degrees application and pockets greater than 7 mm). The results suggest that the oral irrigator will deliver an aqueous solution into periodontal pockets and will penetrate on average to approximately half the depth of the pockets.

An Al0.20Ga0.80As solar cell with a band gap graded from 1.64 eV at the junction to 1.72 eV at the surface has been fabricated using metalorganic chemical vapor deposition. An efficiency of 19.2% has been measured under 1-sun, AM2 simulated conditions with an open circuit voltage of 1.18 V, a short circuit density of 14.5 mA/cm2, and a fill factor of 0.83.

AlGaAs/GaAs heteroface solar concentrator cells which exhibit 26% efficiency at 753 sun (AM1.5, 100 mW/cm2) have been fabricated using metalorganic chemical vapor deposition. Magnesium was used as the dopant in the p-type emitter and selenium was used as the n-type dopant. The design parameters of the solar cell were determined with the aid of a computer program which realistically models the performance of such cells.

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