TY - JOUR
T1 - Gene therapy for the CNS using AAVs
T2 - the impact of systemic delivery by AAV9
AU - Saraiva, Joana
AU - Nobre, Rui Jorge
AU - Pereira de Almeida, Luis
N1 - Funding Information:
Our group is supported by funds from FEDER and the Competitive Factors Operational Program – COMPETE and by national funds through the Portuguese Foundation for Science and Technology ( PTDC/SAU-NMC/116512/2010 , E-Rare4/0003/2012 , PTDC/NEU-NMC/0084/2014 to LPA, EXPL/NEU-NMC/0331/2012 , SFRH/BPD/66705/2009 to RJN); by the JPND cofunding JPCOFUND/0001 and 0005/2015 (LPA) funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement nº 643417, by the Richard Chin and Lily Lock Machado Joseph Disease Research Fund (LPA); and the National Ataxia Foundation (LPA and RJN).
Publisher Copyright:
© 2016 Elsevier B.V.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/11/10
Y1 - 2016/11/10
N2 - 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.
AB - 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.
KW - AAV9
KW - Adeno-associated virus (AAV)
KW - Central nervous system
KW - Gene therapy
KW - Systemic administration
UR - http://www.scopus.com/inward/record.url?scp=84988451695&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.09.011
DO - 10.1016/j.jconrel.2016.09.011
M3 - Review article
C2 - 27637390
AN - SCOPUS:84988451695
SN - 0168-3659
VL - 241
SP - 94
EP - 109
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -