Safe and neuroprotective vectors for long-term traumatic brain injury gene therapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-29

AUTHORS

Daniela Blanco-Ocampo, Fabio Andrés Cawen, Luis Angel Álamo-Pindado, María Luciana Negro-Demontel, Hugo Peluffo

ABSTRACT

Traumatic brain injury (TBI) is a complex and progressive brain injury with no approved treatments that needs both short- and long-term therapeutic strategies to cope with the variety of physiopathological mechanisms involved. In particular, neuroinflammation is a key process modulating TBI outcome, and the potentiation of these mechanisms by pro-inflammatory gene therapy vectors could contribute to the injury progression. Here, we evaluate in the controlled cortical impact model of TBI, the safety of integrative-deficient lentiviral vectors (IDLVs) or the non-viral HNRK recombinant modular protein/DNA nanovector. These two promising vectors display different tropisms, transduction efficiencies, short- or long-term transduction or inflammatory activation profile. We show that the brain intraparenchymal injection of these vectors overexpressing green fluorescent protein after a CCI is not neurotoxic, and interestingly, can decrease the short-term sensory neurological deficits, and diminish the brain tissue loss at 90 days post lesion (dpl). Moreover, only IDLVs were able to mitigate the memory deficits elicited by a CCI. These vectors did not alter the microglial or astroglial reactivity at 90 dpl, suggesting that they do not potentiate the on-going neuroinflammation. Taken together, these data suggest that both types of vectors could be interesting tools for the design of gene therapy strategies targeting immediate or long-term neuropathological mechanisms of TBI. More... »

PAGES

1-8

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41434-019-0073-8

DOI

http://dx.doi.org/10.1038/s41434-019-0073-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113051810

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30926962


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