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  4. Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration

Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration

Scientific Reports, 2017 · DOI: 10.1038/s41598-017-10250-z · Published: August 4, 2017

Regenerative MedicineNeurologyBiomedical

Simple Explanation

The study explores a new way to help damaged nerves regrow by using nanoparticles to deliver a special molecule (siRNA) that reduces the amount of a protein called fidgetin in nerve cells. Fidgetin normally cuts microtubules, which are like tiny support beams inside nerve cells. By reducing fidgetin, the researchers aimed to increase the flexible, 'labile' part of these support beams, which they believe helps nerves grow better. The results showed that this nanoparticle delivery method successfully got the siRNA into nerve cells, reduced fidgetin levels, increased the flexible microtubules, and helped the nerves grow, even in the presence of substances that normally stop nerve growth.

Study Duration
Not specified
Participants
Adult rat dorsal root ganglion neurons in culture
Evidence Level
Level: Not specified, Study type: In vitro experiment

Key Findings

  • 1
    Nanoparticle delivery of fidgetin siRNA increases labile microtubule mass in the axons of cultured rat adult DRG neurons.
  • 2
    Fidgetin knockdown results in increased axonal outgrowth in a manner dependent upon unacetylated tubulin.
  • 3
    Fidgetin knockdown promotes axonal growth on non-permissive substrate.

Research Summary

The study investigates a nanoparticle-based approach to deliver fidgetin siRNA into adult rat DRG neurons to promote nerve regeneration. Results demonstrate that partial knockdown of fidgetin increases labile microtubule mass and enhances axonal growth, even in the presence of growth-inhibitory molecules. The findings suggest that fidgetin knockdown, achieved through nanoparticle delivery of siRNA, is a promising therapeutic strategy for nerve injury and regeneration, offering advantages over microtubule-stabilizing drugs.

Practical Implications

Therapeutic Target

Fidgetin is a promising therapeutic target for nerve injury.

Delivery Platform

Nanoparticle-based platform is a promising mode of delivery for the siRNA.

Clinical Translation

The nanoparticle approach is readily translatable to in vivo studies on animals and ultimately to clinical applications.

Study Limitations

  • 1
    Knockdown of fidgetin is partial with this approach
  • 2
    The level of knockdown and the phenotype were somewhat more modest
  • 3
    adult DRG cultures do not transfect well by conventional methods

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