Display of Self-Peptide on Adeno-Associated Virus Capsid Decreases Phagocytic Uptake .

Adeno-associated virus (AAV) vectors are currently investigated as gene transfer agents for the treatment of a variety of diseases. However, activation of the host immune response upon vector administration limits the use of AAV in the clinical setting. To decrease host detection of AAVs, we tested the CD47-based "don't-eat-me" signal in the context of the AAV capsid.

An essential N-terminal serine-rich motif in the AAV VP1 and VP2 subunits that may play a role in viral transcription.

Adeno-associated virus (AAV) is one of the most researched, clinically utilized gene therapy vectors. Though clinical success has been achieved, transgene delivery and expression may be hindered by cellular and tissue barriers. Understanding the role of receptor binding, entry, endosomal escape, cytoplasmic and nuclear trafficking, capsid uncoating, and viral transcription in therapeutic efficacy is paramount.

Longer Inactivating Sequence in Peptide Lock Improves Performance of Synthetic Protease-Activatable Adeno-Associated Virus.

Adeno-associated viruses (AAVs) are promising gene therapy vectors but may exhibit off-target delivery due to broad tissue tropism. We recently developed a synthetic protease-activatable AAV vector, named provector, that transduces cells preferentially in environments rich in matrix metalloproteinases (MMPs) which are elevated in a variety of diseases, including various cancers and heart diseases. The provector displays peptide locks made up of MMP recognition sites flanking an inactivating sequence (IS) composed of four aspartic acid residues (D4).

Reverse transduction can improve efficiency of AAV vectors in transduction-resistant cells.

Reverse transduction, also known as substrate-mediated gene delivery, is a strategy in which viral vectors are first coated onto a surface that subsequently comes into contact with mammalian cells. The cells internalize the surface-attached vectors, resulting in transgene expression. We hypothesized that forcing the interaction between cells and adeno-associated virus (AAV) vectors through a reverse transduction format would increase in vitro gene delivery efficiencies of the vectors in transduction-resistant cells.

Synthetic virology: engineering viruses for gene delivery.

The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors.