Vectors based on the clade E family member adeno-associated virus (AAV) serotype 8 have shown promise in patients with hemophilia B and have emerged as best in class for human liver gene therapies. We conducted a thorough evaluation of liver-directed gene therapy using vectors based on several natural and engineered capsids including the clade E AAVrh10 and the largely uncharacterized and phylogenically distinct AAV3B. Included in this study was a putatively superior hepatotropic capsid, AAVLK03, which is very similar to AAV3B. Vectors based on these capsids were benchmarked against AAV8 and AAV2 in a number of in vitro and in vivo model systems including C57BL/6 mice, immune-deficient mice that are partially repopulated with human hepatocytes, and nonhuman primates. Our studies in nonhuman primates and human hepatocytes demonstrated high level transduction of the clade E-derived vectors and equally high transduction with vectors based on AAV3B. In contrast to previous reports, AAVLK03 vectors are not superior to either AAV3B or AAV8. Vectors based on AAV3B should be considered for liver-directed gene therapy when administered following, or before, treatment with the serologically distinct clade E vectors.

An experimental and numerical investigation of the two-dimensional flow normal to a flat plate is described. In the experiments, the plate is started impulsively from rest in a channel for Reynolds numbers, based on the breadth of the plate, in the range 5 ≤ Re ≤ 20. Over this range of Re the flow remains symmetrical and stable and tends to a steady state but is shown to depend strongly on the ratio λ of the plate to channel breadth. The evolution of the experimental flow with time and Reynolds number is studied and the variation with λ in the range 0.05 ≤ λ ≤ 0.2 is investigated sufficiently to enable an estimate of properties of the flow as λ → 0 to be obtained for the steady-state flow. The numerical results are obtained for steady flow normal to a flat plate in an unbounded fluid for Reynolds numbers up to Re = 100. They supplement and extend results for this flow obtained for values of Re up to 20 by Hudson & Dennis (1985). The present solutions have been found using a vorticity-stream function formulation rather than the primitive-variable approach of Hudson & Dennis and provide an independent check on these results. A comparison of the theoretical results for Re ≤ 20 with the limit λ → 0 of the experimental results is, generally speaking, extremely satisfactory.

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