Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord

H Peluffo, E Foster, S G Ahmed, N Lago, T H Hutson, L Moon, P Yip, K Wanisch, V Caraballo-Miralles, G Olmos, J Lladó, S B McMahon, R J Yáñez-Muñoz

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Gene transfer to spinal cord cells may be crucial for therapy in spinal muscular atrophy, amyotrophic lateral sclerosis and spinal cord injury. Lentiviral vectors are efficient for transduction of a variety of cells, but like all integrating vectors they pose a risk of insertional mutagenesis. Integration-deficient lentiviral vectors (IDLVs) remain episomal but retain the transduction efficiency of standard integrating lentiviral vectors, particularly when the episomes are not diluted out through repeated cell division. We have now applied IDLVs for transduction of spinal cord in vitro, in explants and in vivo. Our results demonstrate similar efficiency of eGFP expression from integrating lentiviral vectors and IDLVs in most cell types analyzed, including motor neurons, interneurons, dorsal root ganglia (DRG) neurons and astroglia. IDLV-mediated expression of pro-glial-cell-derived neurotrophic factor (Gdnf) rescues motor neuron cultures from death caused by removal of exogenous trophic support. IDLVs also mediate efficient RNA interference in DRG neuron cultures. After intraparenchymal injection in the rat and mouse cervical and lumbar regions in vivo, transduction is mainly neuronal, with both motor neurons and interneurons being efficiently targeted. These results suggest that IDLVs could be efficient and safer tools for spinal cord transduction in future therapeutic strategies.Gene Therapy advance online publication, 18 October 2012; doi:10.1038/gt.2012.78.
Original languageEnglish
JournalGene Therapy,
DOIs
Publication statusE-pub ahead of print - 18 Oct 2012

Fingerprint

Dive into the research topics of 'Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord'. Together they form a unique fingerprint.

Cite this