AAV Vectors Targeted to Oligodendrocytes

Abstract

The invention relates to chimeric AAV capsids targeted to oligodendrocytes, virus vectors comprising the same, and methods of using the vectors to target oligodendrocytes.

1 - 27 . (canceled) 
     
     
         28 . A method of delivering a nucleic acid of interest to an oligodendrocyte, the method comprising contacting the oligodendrocyte with an AAV particle comprising:
 an AAV vector genome comprising or encoding the nucleic acid of interest; and   an AAV capsid comprising the amino acid sequence of one of SEQ ID NOS:2-4, wherein 25 or fewer amino acids are substituted, deleted, and/or inserted, wherein the AAV capsid encapsidates the AAV vector genome.   
     
     
         29 . A method of delivering a nucleic acid of interest to an oligodendrocyte in a mammalian subject, the method comprising:
 administering an effective amount of an AAV particle comprising   an AAV vector genome comprising or encoding the nucleic acid of interest; and an AAV capsid comprising the amino acid sequence of one of SEQ ID NOS:2-4, wherein 25 or fewer amino acids are substituted, deleted, and/or inserted, wherein the AAV capsid encapsidates the AAV vector genome, or a pharmaceutical formulation comprising the AAV particle to a mammalian subject.   
     
     
         30 . The method of  claim 29 , wherein the mammalian subject is a human subject. 
     
     
         31 . The method of  claim 29 , wherein the AAV particle is delivered to the central nervous system (CNS). 
     
     
         32 . The method of  claim 31 , wherein the AAV particle is delivered directly to the CNS by intrathecal, intracerebral, intraventricular, intranasal, intra-aural, intra-ocular, or peri-ocular delivery, or any combination thereof. 
     
     
         33 . The method of  claim 31 , wherein the subject has a compromised blood brain barrier and the AAV particle is delivered to the CNS by intravenous administration. 
     
     
         34 . 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 an effective amount of an AAV particle comprising:   an AAV vector genome comprising or encoding the nucleic acid of interest; and an AAV capsid comprising the amino acid sequence of one of SEQ ID NOS:2-4, wherein 25 or fewer amino acids are substituted, deleted, and/or inserted, wherein the AAV capsid encapsidates the AAV vector genome, or a pharmaceutical formulation comprising the AAV particle to a mammalian subject.   
     
     
         35 . A method of treating a disorder associated with oligodendrocyte dysfunction in a mammalian subject in need thereof, the method comprising administering a therapeutically effective amount of an AAV particle comprising:
 an AAV vector genome; and   an AAV capsid comprising the amino acid sequence of one of SEQ ID NOS:2-4, wherein 25 or fewer amino acids are substituted, deleted, and/or inserted, wherein the AAV capsid encapsidates the AAV vector genome, or a pharmaceutical formulation comprising the AAV particle to a mammalian subject.   
     
     
         36 . The method of  claim 35 , wherein the disorder associated with oligodendrocyte dysfunction is a demyelinating disease. 
     
     
         37 . The method of  claim 35 , wherein the disorder associated with oligodendrocyte dysfunction is multiple sclerosis, Pelizaeus-Merzbacher disease, Krabbe's disease, metachromatic leukodystrophy, adrenoleukodystrophy, Canavan disease, Alexander disease, orthochromatic leukodystrophy, Zellweger disease, 18q-syndrome, cerebral palsy, spinal cord injury, traumatic brain injury, stroke, phenylketonuria, or viral infection. 
     
     
         38 - 39 . (canceled) 
     
     
         40 . The method of  claim 28 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4, wherein 10 or fewer amino acids are substituted, deleted, and/or inserted. 
     
     
         41 . The method of  claim 28 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4. 
     
     
         42 . The method of  claim 29 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4, wherein 10 or fewer amino acids are substituted, deleted, and/or inserted. 
     
     
         43 . The method of  claim 29 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4. 
     
     
         44 . The method of  claim 34 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4, wherein 10 or fewer amino acids are substituted, deleted, and/or inserted. 
     
     
         45 . The method of  claim 34 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4. 
     
     
         46 . The method of  claim 35 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4, wherein 10 or fewer amino acids are substituted, deleted, and/or inserted. 
     
     
         47 . The method of  claim 35 , wherein the AAV capsid comprises the amino acid sequence of one of SEQ ID NOS:2-4.