Capsid Proteins Optimize Delivery of Therapeutic Genes to Targeted Tissues
These variant recombinant adeno-associated virus (rAAV) particles feature capsid surface proteins that focus delivery of therapeutic genes toward specific tissues, decreasing uptake in non-target tissues. Demand for the AAV gene therapy delivery platform is rapidly increasing as a result of its low pathogenicity and stable transgene expression. Projections value the global gene therapy market at $6.6 billion by 2027 . Gene therapy has many clinical applications for the treatment of rare and terminal human diseases. However, with certain systemic diseases, ensuring the genes get into the right tissues requires a high concentration of AAV vectors, which can cause potentially life-threatening immune responses in patients. Available viral vectors do not adequately target specific tissues.
Researchers at the University of Florida have developed rAAV capsid variants that can increase or decrease uptake of the therapeutic gene particles in a certain tissue of interest. This improved tissue targeting allows for more efficient transgene delivery while reducing the chance of off-target effects.
Application
AAV capsid variants that optimize delivery of gene therapies to target tissues, such as skeletal muscle, central nervous system, or cardiac tissues
Advantages
- Alters the viral protein structure, improving AAV particles’ ability to target specific tissues
- Reduces the amount of virus required, minimizing the chance of undesirable side effects
- Increases efficiency of packed gene therapy particles, decreasing dosages to lower production costs
Technology
These altered rAAV capsids have amino acid substitutions that change their surface protein structure to enhance and/or reduce their tendency toward uptake in certain tissues. This creates a viral vector platform capable of more efficient transduction when delivering therapeutic genes to treat a variety of diseases. Researchers at the University of Florida have tested their variant rAAV particles with altered capsids in skeletal, cardiac, and muscle cells, and have observed improved cell uptake as well as encoded protein production that exceeds that of available synthetic variants.
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