1. A Localized Materials-Based Strategy to Non-Virally Deliver Chondroitinase ABC mRNA Improves Hindlimb Function in a Rat Spinal Cord Injury Model.
- Author
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Khalil AS, Hellenbrand D, Reichl K, Umhoefer J, Filipp M, Choe J, Hanna A, and Murphy WL
- Subjects
- Animals, Chondroitin Sulfate Proteoglycans metabolism, Chondroitin Sulfate Proteoglycans therapeutic use, Gliosis drug therapy, Hindlimb pathology, Nerve Regeneration, RNA, Messenger genetics, Rats, Rats, Sprague-Dawley, Spinal Cord pathology, Chondroitin ABC Lyase metabolism, Chondroitin ABC Lyase pharmacology, Chondroitin ABC Lyase therapeutic use, Spinal Cord Injuries drug therapy, Spinal Cord Injuries pathology
- Abstract
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., (© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
- Published
- 2022
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