A Localized Materials-Based Strategy to Non-Virally Deliver Chondroitinase ABC mRNA Improves Hindlimb Function in a Rat Spinal Cord Injury Model.
biomaterials
messenger RNA delivery
non-viral gene therapy
regenerative medicines
spinal cord injury
Journal
Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
14
07
2022
received:
02
02
2022
pubmed:
27
7
2022
medline:
12
10
2022
entrez:
26
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35882512
doi: 10.1002/adhm.202200206
pmc: PMC10031873
mid: NIHMS1840031
doi:
Substances chimiques
Chondroitin Sulfate Proteoglycans
0
RNA, Messenger
0
Chondroitin ABC Lyase
EC 4.2.2.20
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2200206Subventions
Organisme : National Institute of General Medical Sciences' Biotechnology Training Program
ID : NIH 5 T32 GM008349
Organisme : NIAMS NIH HHS
ID : R01 AR059916
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008692
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109427
Pays : United States
Organisme : NIH HHS
ID : TL1: TL1TR002375
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008349
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002373
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM140935
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB019558
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR002375
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR002383
Pays : United States
Informations de copyright
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
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