Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB).
Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB).
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DOI：
10.1038/mt.2009.292
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发表时间：
2010-03
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影响因子：
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DNA shuffling and directed evolution were employed to develop a novel adeno-associated virus (AAV) vector capable of crossing the seizure-compromised blood–brain barrier (BBB) and transducing cells in the brain. Capsid DNA from AAV serotypes 1–6, 8, and 9 were shuffled and recombined to create a library of chimeric AAVs. One day after kainic acid–induced limbic seizure activity in rats, the virus library was infused intravenously (i.v.), and 3 days later, neuron-rich cells were mechanically dissociated from seizure-sensitive brain sites, collected and viral DNA extracted. After three cycles of selection, green fluorescent protein (GFP)–packaged clones were administered directly into brain or i.v. 1 day after kainic acid–induced seizures. Several clones that were effective after intracranial administration did not transduce brain cells after the i.v. administration. However, two clones (32 and 83) transduced the cells after direct brain infusion and after i.v. administration transduced the cells that were localized to the piriform cortex and ventral hippocampus, areas exhibiting a seizure-compromised BBB. No transduction occurred in areas devoid of BBB compromise. Only one parental serotype (AAV8) exhibited a similar expression profile, but the biodistribution of 32 and 83 diverged dramatically from this parental serotype. Thus, novel AAV vectors have been created that can selectively cross the seizure-compromised BBB and transduce cells.
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影响因子：
12.4
作者：
Duque, Sandra;Joussemet, Beatrice;Barkats, Martine
通讯作者：
Barkats, Martine
DOI：
10.1007/978-1-60327-263-6_13
发表时间：
2009-01-01
期刊：
ANIMAL MODELS OF EPILEPSY: METHODS AND INNOVATIONS
影响因子：
--
作者：
Foti, Stacey B.;Russek, Shelley J.;McCown, Thomas J.
通讯作者：
McCown, Thomas J.
影响因子：
12.4
作者：
Towne, Chris;Raoul, Cedric;Aebischer, Patrick
通讯作者：
Aebischer, Patrick
影响因子：
20.3
作者：
Manno, CS;Chew, AJ;Glader, B
通讯作者：
Glader, B
影响因子：
5.4
作者：
Grimm, Dirk;Lee, Joyce S.;Kay, Mark A.
通讯作者：
Kay, Mark A.