Nonviral Gene Delivery to the Central Nervous System Based on a Novel Integrin-Targeting Multifunctional Protein
| Autor: | Hugo Peluffo, Anna Arís, Laia Acarin, Berta González, Bernardo Castellano, Antonio Villaverde |
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| Rok vydání: | 2003 |
| Předmět: |
Central Nervous System
Transgene Blotting Western Genetic Vectors Green Fluorescent Proteins Central nervous system Gene Expression Gene delivery Biology Transfection In vivo Escherichia coli Genetics medicine Animals Transgenes Molecular Biology Microglia Genetic Therapy beta-Galactosidase Immunohistochemistry Rats Cell biology Luminescent Proteins medicine.anatomical_structure Immunology Axoplasmic transport Molecular Medicine Densitometry Astrocyte |
| Zdroj: | Human Gene Therapy. 14:1215-1223 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | Successful introduction of therapeutic genes into the central nervous system (CNS) requires the further development of efficient transfer vehicles that avoid viral vector-dependent adverse reactions while maintaining high transfection efficiency. The multifunctional protein 249AL was recently constructed for in vitro gene delivery. Here, we explore the capability of this vector for in vivo gene delivery to the postnatal rat CNS. Significant transgene expression was observed both in the excitotoxically injured and noninjured brain after intracortical injection of the DNA-contaning-249AL vector. In the injured brain, a widespread expression occurred in the entire lesioned area and retrograde transport of the vector toward distant thalamic nuclei and transgene expression were observed. Neurons, astrocytes, microglia, and endothelial cells expressed the transgene. No recruitment of leukocytes, demyelination, interleukin-1beta expression, or increase in astrocyte/microglial activation was observed at 6 days postinjection. In conclusion, the 249AL vector shows promising properties for gene therapy intervention in the CNS, including the targeting of different cell populations. |
| Databáze: | OpenAIRE |
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