Novel recombinant adeno-associated virus capsids with enhanced human pancreatic tropism
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsKatja Pekrun, Mark A. Kay
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Abstract
The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human pancreatic tissue or human islets as compared non-variant parent capsid polypeptides.
Claims33
A variant adeno-associated virus (AAV) capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human pancreatic tissue or human islets as compared to a non-variant parent capsid polypeptide.
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An adeno-associated virus (AAV) vector comprising a nucleic acid sequence encoding a variant AAV capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human pancreatic tissue or human islets as compared to a non-variant parent capsid polypeptide.
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A method for generating a variant AAV capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human pancreatic tissue or human islets as compared to a non-variant parent capsid polypeptide, said method comprising:
- a) generating a library of variant AAV capsid polypeptide genes, wherein said variant AAV capsid polypeptide genes include a plurality of variant AAV capsid polypeptide genes comprising sequences from more than one non-variant parent capsid polypeptide;
- b) generating an AAV vector library by cloning said variant AAV capsid polypeptide gene library into AAV vectors, wherein said AAV vectors are replication competent AAV vectors;
- c) screening said AAV vector library from b) encoding for variant AAV capsid polypeptides for increased transduction or tropism in human pancreatic tissue or human islets as compared to a non-variant parent capsid polypeptide;
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- d) selecting said variant AAV capsid polypeptides from c).
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An adeno-associated virus (AAV) vector comprising a nucleic acid sequence encoding a variant AAV capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human liver tissue or human hepatocytes as compared to a non-variant parent capsid polypeptide.
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A method for generating a variant AAV capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human liver tissue or human hepatocytes as compared to a non-variant parent capsid polypeptide, said method comprising:
- a) generating a library of variant AAV capsid polypeptide genes, wherein said variant AAV capsid polypeptide genes include a plurality of variant AAV capsid polypeptide genes comprising sequences from more than one non-variant parent capsid polypeptide;
- b) generating an AAV vector library by cloning said variant AAV capsid polypeptide gene library into AAV vectors, wherein said AAV vectors are replication competent AAV vectors;
- c) screening said AAV vector library from b) encoding for variant AAV capsid polypeptides for increased transduction or tropism in human pancreatic tissue or human islets as compared to a non-variant parent capsid polypeptide;
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- d) selecting said variant AAV capsid polypeptides from c).
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Dependencies are inferred from the claim text.