Intracellular expression of an antibody fragment-neutralizing p21 ras promotes tumor regression

Mutated ras genes are found in a large number of human tumors and, therefore, constitute one of the primary targets for cancer treatment. Microinjection of the neutralizing anti-Ras monoclonal antibody Y13-259 was previously reported to induce transient phenotypic reversion of ras-transformed rodent fibroblasts in vitro. We have prepared a single-chain Fv fragment (scFv) derived from Y13-259, and here, we show that intracellular expression of the scFv led to the specific inhibition of the Ras signaling pathway in Xenopus laevis oocytes and NIH3T3 fibroblasts. Moreover, neutralizing Ras with the scFv specifically promoted apoptosis in vitro in human cancer cells but not in untransformed cells. As a step toward cancer gene therapy, we finally demonstrated that intratumor transduction of HCT116 colon carcinoma cells with the anti-Ras scFv using an adenoviral vector elicited sustained tumor regression in nude mice.     

Nanoscale Film Thickness Gradients Printed in Open Air by Spatially Varying Chemical Vapor Deposition

Nanoscale films are integral to all modern electronics. To optimize device performance, researchers vary the film thickness by making batches of devices, which is time-consuming and produces experimental artifacts. Thin films with nanoscale thickness gradients that are rapidly deposited in open air for combinatorial and high-throughput (CHT) studies are presented. Atmospheric pressure spatial atomic layer deposition reactor heads are used to produce spatially varying chemical vapor deposition rates on the order of angstroms per second. ZnO and Al₂O₃ films are printed with nm-scale thickness gradients in as little as 45 s and CHT analysis of a metal-insulator-metal diode and perovskite solar cell is performed. By testing 360 Pt/Al₂O₃/Al diodes with 18 different Al₂O₃ thicknesses on one wafer, a thicker insulator layer (≈7.0 nm) is identified for optimal diode performance than reported previously. Al₂O₃ thin film encapsulation is deposited by atmospheric pressure chemical vapor deposition (AP-CVD) on a perovskite solar cell stack for the first time and a convolutional neural network is developed to analyze the perovskite stability. The rapid nature of AP-CVD enables thicker films to be deposited at a higher temperature than is practical with conventional methods. The CHT analysis shows enhanced stability for 70 nm encapsulation films.