Recombinant adeno-associated vectors for targeted treatment
AssigneeCity of Hope
InventorsSaswati Chatterjee, Laura Smith, Kamehameha Wong
Life of this patent
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Abstract
Novel adeno-associated virus (AAV) vectors in nucleotide and amino acid forms and uses thereof are provided. The isolates show specific tropism for certain target tissues, such as blood stem cells, liver, heart and joint tissue, and may be used to transduce stem cells for introduction of genes of interest into the target tissues. Certain of the vectors are able to cross tightly controlled biological junctions, such as the blood-brain barrier, which open up additional novel uses and target organs for the vectors, providing for additional methods of gene therapy and drug delivery.
Claims15
A method of treating a neurological disease or disorder in a subject, comprising systemically administering an AAV vector capable of crossing the blood-brain barrier to the subject, said vector comprising:
- (a) a recombinant nucleotide sequence which encodes an amino acid sequence of an AAV capsid or modified VP1, VP2, or VP3 portion thereof, wherein said amino acid sequence comprises SEQ ID NO:1 having one or more amino acid substitutions, and wherein the one or more amino acid substitutions comprise (i) an alanine (A) at position 346 in lieu of threonine (T), (ii) an arginine (R) at position 505 in lieu of a glycine (G), or (iii) both (i) and (ii);
- and
- (b) one or more therapeutic nucleotide sequences which encode one or more therapeutic agents for treating the neurological disease or disorder, wherein the one or more therapeutic nucleotide sequences are heterologous to the AAV vector;
- wherein the neurological disease or disorder is a disease or disorder of the brain;
- and
- wherein the vector is able to cross the intact blood-brain barrier and transduce a target cell or tissue in the brain with the one or more therapeutic nucleotide sequences, thereby delivering said therapeutic agent to treat the disease or disorder of the brain.
A method of treating a disease or disorder of the brain in a subject, comprising systemically administering an AAVHSC15 vector capable of crossing the blood-brain barrier to the subject, said vector comprising:
- (a) a recombinant nucleotide sequence which encodes an amino acid sequence comprising SEQ ID NO:16;
- and
- (b) one or more therapeutic nucleotide sequences which encode one or more therapeutic agents for treating the disease or disorder of the brain, wherein the one or more therapeutic nucleotide sequences are heterologous to the AAVHC15 vector;
- wherein the vector is able to cross the intact blood-brain barrier and permanently or transiently transduce a target brain cell or tissue with the one or more therapeutic nucleotide sequences, thereby delivering said therapeutic agent to treat the disease or disorder of the brain.
A method of treating a neurological disease or disorder in a subject, comprising systemically administering an AAV vector capable of crossing the blood-brain barrier to the subject, said vector comprising:
- (a) a recombinant nucleotide sequence comprising SEQ ID NO:33;
- and
- (b) one or more therapeutic nucleotide sequences which encode one or more therapeutic agents, wherein the one or more therapeutic nucleotide sequences are heterologous to AAV;
- wherein the neurological disease or disorder is a disease or disorder of the brain;
- and
- wherein the vector is able to cross the intact blood-brain barrier and transduce a target cell or tissue in the brain with the one or more therapeutic nucleotide sequences, thereby delivering said therapeutic agent to treat the disease or disorder of the brain.
Dependencies are inferred from the claim text.