Nevue Alexander A, Sairavi Anusha, Huang Samuel J, Nakai Hiroyuki, Mello Claudio V
Department of Behavioral Neuroscience, Oregon Health & Science University, Oregon, USA.
Department of Molecular and Medical Genetics, Oregon Health & Science University, Oregon, USA.
bioRxiv. 2024 May 17:2024.05.16.589954. doi: 10.1101/2024.05.16.589954.
The G protein-coupled receptor 108 () gene encodes a protein factor identified as critical for adeno-associated virus (AAV) entry into mammalian cells, but whether it is universally involved in AAV transduction is unknown. Remarkably, we have discovered that is absent in the genomes of birds and in most other sauropsids, providing a likely explanation for the overall lower AAV transduction efficacy of common AAV serotypes in birds compared to mammals. Importantly, transgenic expression of human and manipulation of related glycan binding sites in the viral capsid significantly boost AAV transduction in zebra finch cells. These findings contribute to a more in depth understanding of the mechanisms and evolution of AAV transduction, with potential implications for the design of efficient tools for gene manipulation in experimental animal models, and a range of gene therapy applications in humans.
G蛋白偶联受体108（）基因编码一种蛋白质因子，该因子被确定为腺相关病毒（AAV）进入哺乳动物细胞的关键因素，但它是否普遍参与AAV转导尚不清楚。值得注意的是，我们发现鸟类和大多数其他蜥形纲动物的基因组中不存在，这可能解释了与哺乳动物相比，常见AAV血清型在鸟类中的整体AAV转导效率较低的原因。重要的是，人在斑马雀细胞中的转基因表达以及病毒衣壳中相关聚糖结合位点的操纵显著提高了AAV转导。这些发现有助于更深入地理解AAV转导的机制和进化，对实验动物模型中基因操作高效工具的设计以及人类一系列基因治疗应用具有潜在意义。
