Recombinant adeno-associated viral (AAV) vectors are frequently used to deliver DNA into cells and are currently the leading platform for therapeutic gene delivery in humans. Presently, there is a need for optimized AAV vectors with improved transduction efficiencies in target tissues. In these studies, an engineered albumin-binding consensus domain (ABDCon) peptide was incorporated into the AAV9 capsid via fusion to the N-terminus of the AAV9 VP2 capsid protein to generate a variant AAV9 capsid with albumin-binding properties. The variant capsid, called AAV9-ABDCon, formed viable genome-containing vector particles and exhibited binding to human serum albumin. The AAV9 capsid, on the other hand, was not found to bind to human serum albumin by the methods used in this study. In C57BL/6J mice, AAV9-ABDCon achieved significantly higher levels of liver transduction compared with AAV9 following intravenous administration. These findings show that incorporation of the ABDCon peptide into the capsid VP2 N-terminus may be a potential method to augment AAV-mediated liver-directed gene delivery.

重组腺相关病毒 (AAV) 载体经常用于将 DNA 递送到细胞中，并且目前是人类治疗性基因递送的领先平台。目前，需要优化的 AAV 载体在靶组织中具有改进的转导效率。在这些研究中，工程化的白蛋白结合共有域 (ABDCon) 肽通过与 AAV9 VP2 衣壳蛋白的 N 端融合而被整合到 AAV9 衣壳中，以产生具有白蛋白结合特性的变体 AAV9 衣壳。这种称为 AAV9-ABDCon 的变异衣壳形成了含有基因组的可行载体颗粒，并表现出与人血清白蛋白的结合。另一方面，通过本研究中使用的方法，未发现 AAV9 衣壳与人血清白蛋白结合。在 C57BL/6J 小鼠中，与静脉给药后的 AAV9 相比，AAV9-ABDCon 实现了显着更高的肝脏转导水平。这些发现表明，将 ABDCon 肽掺入衣壳 VP2 N 端可能是增强 AAV 介导的肝脏定向基因传递的潜在方法。