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Journal article
Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration
Scientific reports, v 7(1), pp 9675-10
29 Aug 2017
PMID: 28852085
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration
- Creators
- Timothy O. Austin - Drexel UniversityAndrew J. Matamoros - Drexel UniversityJoel M. Friedman - Albert Einstein College of MedicineAdam J. Friedman - George Washington UniversityParimala Nacharaju - Albert Einstein College of MedicineWenqian Yu - Drexel UniversityDavid J. Sharp - Albert Einstein College of MedicinePeter W. Baas - Drexel University
- Publication Details
- Scientific reports, v 7(1), pp 9675-10
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- 259350 / Craig H. Neilsen Foundation R01 NS28785; R01 GM109909; P01-HL110900 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01HL110900 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01GM109909 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) W81XWH1210379 / Telemedicine and Advanced Technology Research Center (TATRC) at the U.S. Army Medical Research and Materiel Command (USAMRMC); U.S. Army Medical Research & Materiel Command (USAMRMC) 1002809 / National Science Foundation Graduate Research Fellowship; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000408535700020
- Scopus ID
- 2-s2.0-85028454028
- Other Identifier
- 991019167441704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences