In this review, we focus on recent advances in crossing the blood-brain barrier with AAV vectors. We first review the AAV serotypes that can be applied to treating CNS diseases. Recent progress in possible AAV crossing the BBB and transduction mechanisms are then summarized.

2024年9月8日 · a Left: Arraying AAV capsid-specific hits by human brain endothelial cell expression levels reveals highly-conserved LRP6 as a potential receptor for BBB crossing. Right: the LRP6 extracellular...

2024年7月3日 · 因此，科学家们通过工程化改造和筛选，开发了一系列能够有效跨越BBB的AAV血清型，以便更有效地治疗中枢神经系统（CNS）疾病。 AAV9 和 AAV-rh10 都是目前已知可以穿过BBB的天然AAV血清型，在小鼠模型和非人灵长类动物中均显示出有效的基因传递能力，然而，它们的跨BBB的穿透性较低，需要高剂量的AAV才能到达靶细胞，且大量的载体会被其他组织吸收，导致不同程度的不良反应。 加州理工学院的Viviana Gradinaru团队与合作者基于AAV9改 …

2022年10月10日 · We report an adeno-associated virus vector with an enhanced ability to cross the blood–brain barrier in both rodents and non-human primates, and use it to develop systemic anti-tumour gene...

2020年11月17日 · Most reports focus on the ability of AAV to transduce brain parenchymal cells after intravascular injection, and seldom examine the mechanism by which AAV crosses the BBB. Fu and McCarty ( 2016 ) described two ways to transport viral vectors across the BBB: receptor-mediated transcytosis (RMT) and disruption of the BBB (Fig. 3 ).

2024年5月17日 · 该研究开发了一种新型AAV基因治疗递送载体——BI-hTFR1，通过与人血脑屏障中高表达的人转铁蛋白受体（hTfR1）结合，能够有效穿越血脑屏障，将这种AAV注射到表达人转铁蛋白受体（TfR1）的人源化小鼠的血液中，其进入大脑的水平远高于FDA批准的用于中枢神经系统基因治疗的AAV9（高出40-50倍）。 由于该AAV载体是与与血脑屏障中已经过充分研究的TfR1蛋白结合发挥作用，因此，该载体很有可能对人类患者有效，这也为更有效的中枢神经系 …

2021年5月10日 · We discuss the BBB-crossing AAV vectors that have been developed to date and their development methods and provide a systematic research direction to develop more efficient BBB-crossing AAVs to treat CNS diseases as a gene delivery tool. The BBB is composed of cerebral capillaries and various components of the neurovascular unit.

3、修复糖萼有望恢复 bbb 屏障并改善神经功能 在小鼠实验中，通过aav介导在大脑内皮细胞中过表达核心黏蛋白 o-聚糖相关酶，能在显著程度上修复 bbb 渗漏，并让衰老小鼠在空间记忆、条件恐惧等认知行为学指标上得到提升（文章图5）。这表明针对糖萼进行干预 ...

One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide.

2023年6月8日 · Here, we show that a single amino acid substitution (from Q to N) in the BR1 capsid at position 587 (designated BR1N) confers a significantly higher blood-brain barrier (BBB) penetration capacity to BR1. Intravenously infused BR1N showed significantly higher CNS tropism than BR1 and AAV9.