Kwang Il Ryom, Anindita Basu, Debora Stendardi, Elisa Ciaramelli, Alessandro Treves
Taking time to compose thoughts with prefrontal schemata
Experimental brain research
genetic modification capsid proteins peptide insertion created possibility using adenoassociated viral aav vectors receptor specific gene transfer aav targeting common site used insertion aav serotype 2 capsids amino acid positions 587 588 located second highest capsid protrusion reasoning peptide insertions exposed position augments target receptor interaction explored position 453 new insertion site position 453 identified silico capsid mutants carrying model ligand rgd4c position 453 without r585ar588a substitutions compared respective mutants carrying ligand position 587 accessibility inserted ligand determined enzymelinked immunosorbent assay whereas transduction efficiency specificity receptor binding assayed gene transfer competition experiments respectively vector biodistribution determined mice quantitative polymerase chain reaction analysis initially rgd4c inserted position 453 failed efficiently bind target receptor r585 r588 located neighboring peak known mediate primary receptor binding identified interfering residues r585a r588a substitutions rendered position 453 mutants superior ligand position 587 target receptor binding cell transduction efficiency vivo biodistribution independent insertion site directed inserted ligand primary receptor binding avoided position 453 emerged prominent site development targeting mutants furthermore show first time linearly distant residues critical efficiency inserted peptide ligands