Premium
A Localized Materials‐Based Strategy to Non‐Virally Deliver Chondroitinase ABC mRNA Improves Hindlimb Function in a Rat Spinal Cord Injury Model
Author(s) -
Khalil Andrew S.,
Hellenbrand Daniel,
Reichl Kaitlyn,
Umhoefer Jennifer,
Filipp Mallory,
Choe Joshua,
Hanna Amgad,
Murphy William L.
Publication year - 2022
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202200206
Subject(s) - hindlimb , spinal cord injury , spinal cord , messenger rna , function (biology) , medicine , microbiology and biotechnology , neuroscience , chemistry , biology , anatomy , biochemistry , gene
Spinal cord injury often results in devastating consequences for those afflicted, with very few therapeutic options. A central element of spinal cord injuries is astrogliosis, which forms a glial scar that inhibits neuronal regeneration post‐injury. Chondroitinase ABC (ChABC) is an enzyme capable of degrading chondroitin sulfate proteoglycan (CSPG), the predominant extracellular matrix component of the glial scar. However, poor protein stability remains a challenge in its therapeutic use. Messenger RNA (mRNA) delivery is an emerging gene therapy technology for in vivo production of difficult‐to‐produce therapeutic proteins. Here, mineral‐coated microparticles as an efficient, non‐viral mRNA delivery vehicles to produce exogenous ChABC in situ within a spinal cord lesion are used. ChABC production reduces the deposition of CSPGs in an in vitro model of astrogliosis, and direct injection of these microparticles within a glial scar forces local overexpression of ChABC and improves recovery of motor function seven weeks post‐injury.