Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration.
Sci Rep
; 7(1): 9675, 2017 08 29.
Article
en En
| MEDLINE
| ID: mdl-28852085
ABSTRACT
Microtubule-stabilizing drugs have gained popularity for treating injured adult axons, the rationale being that increased stabilization of microtubules will prevent the axon from retracting and fortify it to grow through inhibitory molecules associated with nerve injury. We have posited that a better approach would be not to stabilize the microtubules, but to increase labile microtubule mass to levels more conducive to axonal growth. Recent work on fetal neurons suggests this can be accomplished using RNA interference to reduce the levels of fidgetin, a microtubule-severing protein. Methods to introduce RNA interference into adult neurons, in vitro or in vivo, have been problematic and not translatable to human patients. Here we show that a novel nanoparticle approach, previously shown to deliver siRNA into tissues and organs, enables siRNA to gain entry into adult rat dorsal root ganglion neurons in culture. Knockdown of fidgetin is partial with this approach, but sufficient to increase the labile microtubule mass of the axon, thereby increasing axonal growth. The increase in axonal growth occurs on both a favorable substrate and a growth-inhibitory molecule associated with scar formation in injured spinal cord. The nanoparticles are readily translatable to in vivo studies on animals and ultimately to clinical applications.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Portadores de Fármacos
/
Fármacos Neuroprotectores
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ARN Interferente Pequeño
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Nanopartículas
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ATPasas Asociadas con Actividades Celulares Diversas
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Proteínas Asociadas a Microtúbulos
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Microtúbulos
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos