Department of Immunology, Jiangsu University, Zhenjiang 212013, China.
Department of Immunology, Jiangsu University, Zhenjiang 212013, China; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Life Sci. 2021 Apr 1;270:119142. doi: 10.1016/j.lfs.2021.119142. Epub 2021 Jan 30.
Adeno-associated virus (AAV) vector, an excellent gene therapy vector, has been widely used in the treatment of various central nervous system (CNS) diseases. Due to the presence of the blood-brain barrier (BBB), early attempts at AAV-based CNS diseases treatment were mainly performed through intracranial injections. Subsequently, systemic injections of AAV9, the first AAV that was shown to have BBB-crossing ability in newborn and adult mice, were assessed in clinical trials for multiple CNS diseases. However, the development of systemic AAV injections to treat CNS diseases is still associated with many challenges, such as the efficiency of AAV in crossing the BBB, the peripheral toxicity caused by the expression of AAV-delivered genes, and the immune barrier against AAV in the blood. In this review, we will introduce the biology of the AAV vector and the advantages of systemic AAV injections to treat CNS diseases. Most importantly, we will introduce the challenges associated with systemic injection of therapeutic AAV in treating CNS diseases and suggest feasible solutions.
腺相关病毒（AAV）载体是一种出色的基因治疗载体，已广泛应用于治疗各种中枢神经系统（CNS）疾病。由于血脑屏障（BBB）的存在，早期基于 AAV 的 CNS 疾病治疗主要通过颅内注射进行。随后，在临床试验中评估了具有 BBB 穿越能力的首个 AAV9（AAV9）在新生和成年小鼠中的全身注射，用于多种 CNS 疾病的治疗。然而，利用全身 AAV 注射来治疗 CNS 疾病仍然存在许多挑战，例如 AAV 穿越 BBB 的效率、AAV 递送基因表达引起的外周毒性以及血液中针对 AAV 的免疫屏障。在这篇综述中，我们将介绍 AAV 载体的生物学特性以及全身 AAV 注射治疗 CNS 疾病的优势。最重要的是，我们将介绍与治疗性 AAV 全身注射治疗 CNS 疾病相关的挑战，并提出可行的解决方案。
