AAV vectors encoding NF1 and uses thereof
AssigneeUniversity of Massachusetts
InventorMiguel Sena Esteves
Life of this patent
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Abstract
Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1 (NF1) protein (e.g., mini-NF1 protein and/or full-length NF1 protein) to target cell (e.g., cells and/or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and/or full-length NF1 protein) or variants thereof.
Claims29
A recombinant adeno-associated virus (rAAV) comprising:
- (i) an isolated nucleic acid comprising a transgene, wherein the transgene comprises a nucleotide sequence encoding a mini-neurofibromin (mini-NF1) protein, wherein the mini-NF1 protein comprises:
- (a) a GTPase-activating protein (GAP)-related domain (GRD) and a CRAL-TRIO domain;
- or
- (b) a GTPase-activating protein (GAP)-related domain (GRD) and a CRAL-TRIO domain and a bipartite phospholipid binding domain;
- and
- (ii) an AAV capsid protein.
A 5′ recombinant adeno-associated virus (rAAV) comprising:
- (i) a 5′ isolated nucleic acid flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the isolated nucleic acid comprises, from 5′ to 3′, a promoter operably linked to a nucleotide sequence encoding a first portion of NF1 protein, and a nucleotide sequence encoding a splice donor of an intron;
- and
- (ii) an AAV capsid protein.
A 3′ recombinant adeno-associated virus (rAAV) comprising:
- (i) a 3′ isolated nucleic acid flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the isolated nucleic acid comprises, from 5′ to 3′, a nucleotide sequence encoding a splice acceptor of an intron, and a nucleotide sequence encoding a second portion of NF1 protein;
- and
- (ii) an AAV capsid protein.
A dual vector system comprising:
- (i) a 5′ rAAV comprising:
- (a) a 5′ isolated nucleic acid flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the isolated nucleic acid comprises, from 5′ to 3′, a promoter operably linked to a nucleotide sequence encoding a first portion of NF1 protein, a nucleotide sequence encoding a splice donor of an intron;
- and (b) an AAV capsid protein;
- and
- (ii) a 3′ rAAV comprising:
- (a) a 3′ isolated nucleic acid flanked by adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the isolated nucleic acid comprises, from 5′ to 3′, a nucleotide sequence encoding a splice acceptor of an intron, and a nucleotide sequence encoding a second portion of NF1 protein;
- and (b) an AAV capsid protein.
Dependencies are inferred from the claim text.