Adenovirus type 5 (Ad) based vectors transduce vascular endothelial cells (EC) and have been widely used for vascular gene transfer. However, many cell types express the Ad receptor (cox-sackievirus adenovirus receptor; CAR), preventing selective EC infection and precluding clinical use. We previously isolated the human EC-binding peptides SIGYPLP and LSNFHSS by phage display and demonstrated by means of a bispecific antibody that SIGYPLP directs efficient, high-level, EC-selective Ad-mediated gene transfer. We now generate genetically modified Ad fiber proteins with selective EC tropism by engineering these peptides into the HI loop of the Ad fiber. SIGYPLP, but not LSNFHSS, enhanced EC selectivity, demonstrating maintenance of peptide-cell binding fidelity upon incorporation into virions. Combining fiber mutations that block CAR binding (detargeting) with SIGYPLP insertion (retargeting) generated a novel Ad vector, AdKO1SIG, in a single component system. AdKO1SIG demonstrated efficient and selective tropism for EC compared with control Ad vectors. This is the first demonstration of genetic incorporation of a novel, mammalian, cell-selective ligand that retains its targeting fidelity in the Ad fiber HI loop, in combination with point mutations that abolish fiber-CAR interaction. This study demonstrates the potential for improving the cell-selectivity and safety of adenoviral vectors.
Objectives This comparative study aimed to determine if total keratometry (TK) from IOLMaster 700 could be applied to conventional formulas to perform IOL power calculation in eyes with previous myopic laser refractive surgery, and to evaluate their accuracy with known post-laser refractive surgery formulas. Methods Sixty-four eyes of 49 patients with previous myopic laser refractive surgery were evaluated 1 month after cataract surgery. A comparison of the prediction error was made between no clinical history post-laser refractive surgery formulas (Barrett True-K, Haigis-L, Shammas-PL) and conventional formulas (EVO, Haigis, Hoffer Q, Holladay I, and SRK/T) using TK values obtained with the optical biometer IOLMaster 700 (Carl Zeiss Meditec), as well as Barrett True-K with TK.
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