The safety and high efficiency of adeno-associated virus (AAV) vectors has facilitated their wide-scale use to deliver therapeutic genes for experimental and clinical purposes in diseases affecting the central nervous system (CNS). AAV1, 2, 5, 8, 9, and rh10 are the most commonly used serotypes for CNS applications. Most AAVs are known to transduce genes predominantly into neurons. However, the precise tropism of AAVs in the dentate gyrus (DG), the region where persistent neurogenesis occurs in the adult brain, is not fully understood. We stereotaxically injected 1.5 × 10¹⁰ viral genomes of AAV2, 5, or rh10 carrying green fluorescent protein (GFP) into the right side of gerbil hippocampus, and performed immunofluorescent analysis using differentiation stage-specific markers 1 week after injection. We found that AAV5 showed a significantly larger number of double-positive cells for GFP and Sox2 in the DG, compared with the AAV2 and rh10 groups. On the contrary, AAVrh10 presented a substantially larger number of double-positive cells for GFP and NeuN in the DG, compared with AAV2 and AAV5. Our findings indicated that AAV5 showed high transduction efficiency to neural stem cells and precursor cells, whereas AAVrh10 showed much higher efficiency to mature neurons in the DG.

中文翻译：

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与 AAV2 和 rh10 相比，AAV5 对沙鼠齿状回中神经干细胞和未成熟神经元的转导效率更高

腺相关病毒 (AAV) 载体的安全性和高效性促进了它们在影响中枢神经系统 (CNS) 疾病的实验和临床目的中提供治疗基因的广泛使用。AAV1、2、5、8、9 和 rh10 是 CNS 应用中最常用的血清型。众所周知，大多数 AAV 主要将基因转导到神经元中。然而，AAV 在齿状回 (DG) 中的精确趋向性，即成人大脑中持续神经发生的区域，尚不完全清楚。我们立体定向注射 1.5 × 10 ¹⁰携带绿色荧光蛋白 (GFP) 的 AAV2、5 或 rh10 病毒基因组进入沙鼠海马右侧，并在注射后 1 周使用分化阶段特异性标记物进行免疫荧光分析。我们发现，与 AAV2 和 rh10 组相比，AAV5 在 DG 中显示出显着更多数量的 GFP 和 Sox2 双阳性细胞。相反，与 AAV2 和 AAV5 相比，AAVrh10 在 DG 中呈现大量的 GFP 和 NeuN 双阳性细胞。我们的研究结果表明，AAV5 对神经干细胞和前体细胞显示出高转导效率，而 AAVrh10 对 DG 中的成熟神经元显示出更高的效率。