Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord
| Autor: | G Olmos, Hugo Peluffo, V. Caraballo-Miralles, Sherif G. Ahmed, Rafael J. Yáñez-Muñoz, Lawrence D. F. Moon, J. Llado, Klaus Wanisch, Thomas H. Hutson, Ping K. Yip, Stephen B. McMahon, Edmund Foster, N Lago |
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| Rok vydání: | 2012 |
| Předmět: |
Virus Integration
Genetic Vectors Gene Expression Mice 03 medical and health sciences Transduction (genetics) 0302 clinical medicine Neurotrophic factors Genetics medicine Glial cell line-derived neurotrophic factor Animals Humans Molecular Biology Spinal cord injury Spinal Cord Injuries 030304 developmental biology 0303 health sciences biology Amyotrophic Lateral Sclerosis Lentivirus Gene Transfer Techniques Spinal muscular atrophy Motor neuron medicine.disease Spinal cord Molecular biology Rats Cell biology Muscular Atrophy Mutagenesis Insertional medicine.anatomical_structure Spinal Cord nervous system GDF7 biology.protein Molecular Medicine 030217 neurology & neurosurgery |
| Zdroj: | Gene Therapy Gene Therapy; Vol 20 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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