title: Perinatal systemic gene delivery using adeno-associated viral vectors.
abstract: Neurodegenerative monogenic diseases often affect tissues and organs beyond the nervous system. An effective treatment would require a systemic approach. The intravenous administration of novel therapies is ideal but is hampered by the inability of such drugs to cross the blood-brain barrier (BBB) and precludes efficacy in the central nervous system. A number of these early lethal intractable diseases also present devastating irreversible pathology at birth or soon after. Therefore, any therapy would ideally be administered during the perinatal period to prevent, stop, or ameliorate disease progression. The concept of perinatal gene therapy has moved a step further toward being a feasible approach to treating such disorders. This has primarily been driven by the recent discoveries that particular serotypes of adeno-associated virus (AAV) gene delivery vectors have the ability to cross the BBB following intravenous administration. Furthermore, safety has been demonstrated after perinatal administration mice and non-human primates. This review focuses on the progress made in using AAV to achieve systemic transduction and what this means for developing perinatal gene therapy for early lethal neurodegenerative diseases.
authors.affiliation: Gene Transfer Technology Group, UCL EGA Institute for Women's Health, University College London London, UK.
authors.forename: Rajvinder
authors.initials: R
authors.lastname: Karda
authors.affiliation: Gene Transfer Technology Group, UCL EGA Institute for Women's Health, University College London London, UK.
authors.forename: Suzanne M K
authors.initials: SM
authors.lastname: Buckley
authors.affiliation: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, National University of Singapore Singapore, Singapore.
authors.forename: Citra N
authors.initials: CN
authors.lastname: Mattar
authors.affiliation: Gene Transfer Technology Group, UCL EGA Institute for Women's Health, University College London London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ng
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, University College London London, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: Massaro
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, University College London London, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hughes
authors.affiliation: Neurosciences Unit, UCL Institute of Child Health, University College London London, UK.
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.affiliation: Gene Transfer Technology Group, UCL EGA Institute for Women's Health, University College London London, UK.
authors.forename: Julien
authors.initials: J
authors.lastname: Baruteau
authors.affiliation: Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.affiliation: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, National University of Singapore Singapore, Singapore.
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
authors.affiliation: Centre for Translational Research - GOSgene, UCL Institute of Child Health, University College London London, UK.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bacchelli
authors.affiliation: Gene Transfer Technology Group, UCL EGA Institute for Women's Health, University College London London, UK ; School of Pathology, University of the Witwatersrand Johannesburg, South Africa.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Waddington
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, University College London London, UK.
authors.forename: Ahad A
authors.initials: AA
authors.lastname: Rahim
keywords: adeno-associated virus; gene therapy; metabolic disease; mouse models; neurodegenerative disease; non-human primates; perinatal; systemic delivery