Magnetic resonance imaging-guided delivery of adeno-associated virus type 2 to the primate brain for the treatment of lysosomal storage disorders.
Magnetic resonance imaging-guided delivery of adeno-associated virus type 2 to the primate brain for the treatment of lysosomal storage disorders.
复制标题
磁共振成像引导将 2 型腺相关病毒递送至灵长类动物大脑，用于治疗溶酶体贮积症。
DOI：
10.1089/hum.2010.040
复制
发表时间：
2010
影响因子：
4.2
通讯作者：
Bankiewicz,KS
中科院分区：
文献类型：
--
作者：
Salegio,EAguilar;Kells,AP;Richardson,RM;Hadaczek,P;Forsayeth,J;Bringas,J;Sardi,SP;Passini,MA;Shihabuddin,LS;Cheng,SH;Fiandaca,MS;Bankiewicz,KS
Gene replacement therapy for the neurological deficits caused by lysosomal storage disorders, such as in Niemann-Pick disease type A, will require widespread expression of efficacious levels of acid sphingomyelinase (ASM) in the infant human brain. At present there is no treatment available for this devastating pediatric condition. This is partly because of inherent constraints associated with the efficient delivery of therapeutic agents into the CNS of higher order models. In this study we used an adeno-associated virus type 2 (AAV2) vector encoding human acid sphingomyelinase tagged with a viral hemagglutinin epitope (AAV2-hASM-HA) to transduce highly interconnected CNS regions such as the brainstem and thalamus. On the basis of our data showing global cortical expression of a secreted reporter after thalamic delivery in nonhuman primates (NHPs), we set out to investigate whether such widespread expression could be enhanced after brainstem infusion. To maximize delivery of the therapeutic transgene throughout the CNS, we combined a single brainstem infusion with bilateral thalamic infusions in naive NHPs. We found that enzymatic augmentation in brainstem, thalamic, cortical, as well subcortical areas provided convincing evidence that much of the large NHP brain can be transduced with as few as three injection sites.
真核病毒载体
影响因子：
6.7
作者：
Y. Gluzman
通讯作者：
Y. Gluzman