AAV CAPSID DESIGNS
The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.
1 . A method for delivering a transgene to a target cell in a subject, the method comprising intracranially administering to the subject a recombinant adeno-associated virus (rAAV) comprising:
(i) an isolated nucleic acid comprising a transgene encoding one or more gene products of interest; and
(ii) an adeno-associated acid (AAV) capsid protein having the sequence set forth in SEQ ID NO: 66.
2 . The method of claim 1 , wherein the intracranial administration comprises intrahippocampal injection.
3 . The method of claim 1 , wherein the target cell is a central nervous system (CNS) cell.
4 . The method of claim 3 wherein the CNS cell is a neuron, oligodendrocyte, astrocyte, or microglial cell.
5 . The method of claim 1 , wherein the subject is a mammal, optionally wherein the mammal is a human.
6 . The method of claim 1 , wherein the subject is characterized by production of anti-AAV2 antibodies.
7 . The method of claim 6 , wherein after administration of the rAAV, the subject does not elicit a neutralizing immune response against the rAAV.
8 . The method of claim 1 , wherein the isolated nucleic acid comprises AAV inverted terminal repeats (ITRs) flanking the transgene.
9 . The method of claim 1 , wherein the nucleic acid sequence encoding the one or more gene products is operably linked to a promoter.
10 . The method of claim 1 , wherein the one or more gene products comprise a protein or an inhibitory nucleic acid.
11 . A method for delivering a transgene to a target cell in a subject, the method comprising intravenously administering to the subject a recombinant adeno-associated virus (rAAV) comprising:
(i) an isolated nucleic acid comprising a transgene encoding one or more gene products of interest; and
(ii) an adeno-associated acid (AAV) capsid protein having the sequence set forth in SEQ ID NO: 66,
wherein the administration results in the rAAV crossing the blood brain barrier (BBB) of the subject.
12 . The method of claim 11 , wherein the target cell is a central nervous system (CNS) cell.
13 . The method of claim 12 wherein the CNS cell is a neuron, oligodendrocyte, astrocyte, or microglial cell.
14 . The method of claim 11 , wherein the administration results in decreased transduction of liver cells relative to administration of an rAAV having an AAV2 capsid protein
15 . The method of claim 11 , wherein the subject is a mammal, optionally wherein the mammal is a human.
16 . The method of claim 11 , wherein the subject is characterized by production of anti-AAV2 antibodies.
17 . The method of claim 16 , wherein after administration of the rAAV, the subject does not elicit a neutralizing immune response against the rAAV.
18 . The method of claim 11 , wherein the isolated nucleic acid comprises AAV inverted terminal repeats (ITRs) flanking the transgene.
19 . The method of claim 11 , wherein the nucleic acid sequence encoding the one or more gene products is operably linked to a promoter.
20 . The method of claim 11 , wherein the one or more gene products comprise a protein or an inhibitory nucleic acid.