Department of Cancer biology and Wake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Wake Forest University, Winston-Salem, NC, 27109, USA.
Sci Rep. 2017 Dec 12;7(1):17428. doi: 10.1038/s41598-017-17393-z.
Adeno-associated virus (AAV) is frequently used to manipulate gene expression in the sensory nervous system for the study of pain mechanisms. Although some serotypes of AAV are known to have nerve tropism, whether AAV can distribute to sensory nerves that innervate the bone or skeletal tissue has not been shown. This information is crucial, since bone pain, including cancer-induced bone pain, is an area of high importance in pain biology. In this study, we found that AAVrh10 transduces neurons in the spinal cord and dorsal root ganglia of immunodeficient mice with higher efficacy than AAV2, 5, 6, 8, and 9 when injected intrathecally. Additionally, AAVrh10 has tropism towards sensory neurons in skeletal tissue, such as bone marrow and periosteum, while it occasionally reaches the sensory nerve fibers in the mouse footpad. Moreover, AAVrh10 has higher tropic affinity to large myelinated and small peptidergic sensory neurons that innervate bone, compared to small non-peptidergic sensory neurons that rarely innervate bone. Taken together, these results suggest that AAVrh10 is a useful gene delivery vector to target the sensory nerves innervating bone. This finding may lead to a greater understanding of the molecular mechanisms of chronic bone pain and cancer-induced bone pain.
腺相关病毒（AAV）常用于操纵感觉神经系统中的基因表达，以研究疼痛机制。虽然已知某些 AAV 血清型具有神经嗜性，但 AAV 是否可以分布到支配骨骼组织的感觉神经中尚未得到证实。这一信息至关重要，因为骨痛，包括癌症引起的骨痛，是疼痛生物学中一个非常重要的领域。在这项研究中，我们发现鞘内注射 AAVrh10 比 AAV2、5、6、8 和 9 更有效地转导免疫缺陷小鼠脊髓和背根神经节中的神经元。此外，AAVrh10 对骨骼组织中的感觉神经元具有亲嗜性，如骨髓和骨膜，而偶尔也会到达小鼠足底的感觉神经纤维。此外，与很少支配骨骼的小非肽能感觉神经元相比，AAVrh10 对支配骨骼的大有髓和小肽能感觉神经元具有更高的亲嗜性。综上所述，这些结果表明 AAVrh10 是一种有用的基因传递载体，可用于靶向支配骨骼的感觉神经。这一发现可能有助于深入了解慢性骨痛和癌症引起的骨痛的分子机制。
