Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors

Antonella Consiglio, Angela Gritti, Diego Dolcetta, Antonia Follenzi, Claudio Bordignon, Fred H. Gage, Angelo Luigi Vescovi, Luigi Naldini

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

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 subventrikular 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.

Original languageEnglish (US)
Pages (from-to)14835-14840
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number41
DOIs
StatePublished - Oct 12 2004

ASJC Scopus subject areas

  • General

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