Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons.
The cross section for deeply virtual Compton scattering in the reaction ep → eγp has been measured with the ZEUS detector at HERA using integrated luminosities of 95.0 pb −1 of e + p and 16.7 pb −1 of e − p collisions. Differential cross sections are presented as a function of the exchanged-photon virtuality, Q 2 , and the centre-of-mass energy, W , of the γ * p system in the region 5 < Q 2 < 100 GeV 2 and 40 < W < 140 GeV. The measured cross sections rise steeply with increasing W . The measurements are compared to QCD-based calculations.
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