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Neuron. 2019 Mar 6;101(5):839-862. doi: 10.1016/j.neuron.2019.02.017.

Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality.

Author information

1
Department of Neurology, The Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA. Electronic address: ehudry@mgh.harvard.edu.
2
Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, MA, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Harvard Program in Therapeutic Science, Harvard University, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; The Broad Institute of Harvard and MIT, Cambridge, MA, USA. Electronic address: luk_vandenberghe@meei.harvard.edu.

Abstract

Gene transfer has long been a compelling yet elusive therapeutic modality. First mainly considered for rare inherited disorders, gene therapy may open treatment opportunities for more challenging and complex diseases such as Alzheimer's or Parkinson's disease. Today, examples of striking clinical proof of concept, the first gene therapy drugs coming onto the market, and the emergence of powerful new molecular tools have broadened the number of avenues to target neurological disorders but have also highlighted safety concerns and technology gaps. The vector of choice for many nervous system targets currently is the adeno-associated viral (AAV) vector due to its desirable safety profile and strong neuronal tropism. In aggregate, the clinical success, the preclinical potential, and the technological innovation have made therapeutic AAV drug development a reality, particularly for nervous system disorders. Here, we discuss the rationale, opportunities, limitations, and progress in clinical AAV gene therapy.

KEYWORDS:

AAV; adeno-associated virus; astrocyte; gene therapy; gene transfer; immunity; nervous system; neuron; vector

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