AAV vectors targeted to oligodendrocytes
AssigneeThe University of North Carolina at Chapel Hill
InventorsThomas McCown, Steven Gray
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Abstract
The invention relates to chimeric AAV capsids targeted to oligodendrocytes and virus vectors comprising the same. The invention further relates to methods of delivering a nucleic acid of interest to an oligodendrocyte in vitro and in vivo, methods of delivering a nucleic acid of interest to an area of the CNS bordering a compromised blood-brain barrier, and methods of treating disorders associated with oligodendrocyte dysfunction using the AAV capsids and virus vectors of the invention.
Claims23
A method of delivering a nucleic acid of interest to an oligodendrocyte, the method comprising directly contacting the oligodendrocyte with an adeno-associated virus (AAV) particle comprising:
- an AAV vector genome comprising or encoding the nucleic acid of interest encapsidated by—an AAV capsid comprising an amino acid sequence at least 96% identical to SEQ ID NOS:
- 2 or 4, that exhibits a preferential tropism for oligodendrocytes as compared to astrocytes, microglia and neurons.
A method of delivering a nucleic acid of interest to an oligodendrocyte in a mammalian subject, the method comprising:
- directly administering to the central nervous system (CNS) of the subject to thereby contact oligodendrocytes within the CNS, an effective amount of a pharmaceutical formulation comprising an adeno-associated virus (AAV) particle comprising:
- an AAV vector genome comprising or encoding the nucleic acid of interest encapsidated by an AAV capsid comprising an amino acid sequence at least 96% identical to SEQ ID NOS:
- 2 or 4, that exhibits a preferential tropism for oligodendrocytes as compared to astrocytes, microglia and neurons.
A method of delivering a nucleic acid of interest to an area of the CNS bordering a compromised blood-brain barrier area in a mammalian subject, the method comprising:
- intravenously administering to the subject with a compromised blood-brain barrier an effective amount of an adeno-associated virus (AAV) particle comprising:
- an AAV vector genome comprising or encoding the nucleic acid of interest encapsidated by an AAV capsid comprising an amino acid sequence at least 96% identical to SEQ ID NOS:
- 2 or 4, that exhibits the ability to cross a compromised blood-brain barrier and a preferential tropism for oligodendrocytes as compared to astrocytes, microglia and neurons.
Dependencies are inferred from the claim text.