Gene therapy for the CNS using AAVs: The impact of systemic delivery by AAV9

J Control Release. 2016 Nov 10;241:94-109. doi: 10.1016/j.jconrel.2016.09.011. Epub 2016 Sep 13.


Several attempts have been made to discover the ideal vector for gene therapy in central nervous system (CNS). Adeno-associated viruses (AAVs) are currently the preferred vehicle since they exhibit stable transgene expression in post-mitotic cells, neuronal tropism, low risk of insertional mutagenesis and diminished immune responses. Additionally, the discovery that a particular serotype, AAV9, bypasses the blood-brain barrier has raised the possibility of intravascular administration as a non-invasive delivery route to achieve widespread CNS gene expression. AAV9 intravenous delivery has already shown promising results for several diseases in animal models, including lysosomal storage disorders and motor neuron diseases, opening the way to the first clinical trial in the field. This review presents an overview of clinical trials for CNS disorders using AAVs and will focus on preclinical studies based on the systemic gene delivery using AAV9.

Keywords: AAV9; Adeno-associated virus (AAV); Central nervous system; Gene therapy; Systemic administration.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsid Proteins / genetics
  • Central Nervous System Diseases / genetics
  • Central Nervous System Diseases / therapy*
  • Clinical Trials as Topic
  • Dependovirus / genetics*
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Humans


  • Capsid Proteins