Open AccessRobust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors
Author(s) -
Antonella Consiglio,
Angela Gritti,
Diego Dolcetta,
Antonia Follenzi,
Claudio Bordig,
Fred H. Gage,
Angelo L. Vescovi,
Luigi Naldini
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0404180101
Subject(s) - neural stem cell , subventricular zone , biology , transduction (biophysics) , stem cell , viral vector , microbiology and biotechnology , population , adult stem cell , neuroscience , cellular differentiation , gene , genetics , medicine , recombinant dna , biochemistry , environmental health
Stable genetic modification of adult stem cells is fundamental for both developmental studies and therapeutic purposes. Using in vivo marking studies, we showed that injection of lentiviral vectors (LVs) into the subventricular zone of the adult mouse brain enables efficient gene transfer into long-term self-renewing neural precursors and steady, robust vector expression in their neuronal progeny throughout the subventricular zone and its rostral extension, up to the olfactory bulb. By clonal and population analysis in culture, we proved that in vivo-marked neural precursors display self-renewal and multipotency, two essential characteristics of neural stem cells (NSCs). Thus, LVs efficiently target long-term repopulating adult NSCs, and the effect of the initial transduction is amplified by the continuous generation of NSC-derived, transduced progeny. LVs may thus allow novel studies on NSCs' physiology in vivo, and introduction of therapeutic genes into NSCs may allow the development of novel approaches for untreatable CNS diseases.