Synthetic AAV Capsid Library for Targeted Gene Therapy with Improved Treatment Efficacy

Capsid Library Allows for Gene Therapy Vectors to Target Specific Organs and Tissues

This adeno-associated virus (AAV) capsid library allows for targeted gene therapy to specific organs and tissues. Gene therapy is a burgeoning market within the pharmaceutical industry, with a market value projected to reach $500 million by 2020. AAV derived vectors are promising for human gene therapy applications because they are non-pathogenic. However, their lack of specificity and susceptibility to neutralization by antibodies limits their efficacy. University of Florida researchers developed an AAV capsid library that surpasses current AAV gene therapy treatments and their current issues with neutralization susceptibility and treatment efficacy. The capsid library allows the virus to effectively target specific tissues and organs by fitting to the particular cell type that requires treatment. This increased specificity helps to reduce the chance of an off-target delivery of the virus and is useful in introducing nucleic acid molecules into the selected target cells.

Application

Targeted gene therapy to improve treatment efficacy

Advantages

• Requires low injection dose, lowering production cost and enhancing patient safety and comfort
• Increases transduction efficiency in targeted tissue, improving treatment efficacy
• Reduces off-target delivery, minimizing unintended side effects

Technology

The capsid library uses a gene synthesis-based approach that only alters the amino acid residues that have side chains exposed to the capsid surface. This allows for the restriction of diversity to naturally occurring variants, which improves compatibility with capsid structure and function and increases the probability of generating useful variants. Gene synthesis allows for virtual recombination between naturally occurring sequences at the nucleotide level--producing unique combinations that are unobtainable through other methods. Researchers at the University of Florida tested the synthetic capsid library on mice and discovered the production of AAV variants that transduced a mouse liver with 200 times the efficiency of the original AAV.