Dr Weber was recruited to the Research Center in 2008 as an assistant professor in medicine. He is an expert in the biology of adeno-associated vector entry. He will be heading the vector core for the Research Center for production of AAV and cardiotropic AAV.

Current Research

Altering AAV Tropism with Genetically Modified Capsids

• (Point) Mutations
  • Elimination of Natural Tropism
• Insertion
  • Peptide ligands against specific receptors
  • Peptide Libraries
  • Sequence Replacement

In general, modifications are present in all capsid proteins resulting in reduced viral infectivity

Potential solution: Using capsids that are composed of wildtype-tropism-negative capsid proteins and capsid proteins with a targeting moiety

Using AAV Mosaics To Target Specific Receptors

• Produce AAV virions that are composed of wildtype-tropism- negative capsid proteins and capsid proteins containing an antibody-binding fragment of protein A
• Use a targeting antibody against receptor of choice to alter AAV tropism

Targeting rAAV to c-kit Expressing Cells

• c-kit is highly expressed on on stem cells, including long-term repopulating hematopoietic stem cells and cardiac stem cells
• Targeting rAAV to c-kit can be achieved either with a biotinylated antibody or with biotinylated c-kit ligand (aka stem cell factor [SCF])