Inhibition of craniosynostosis and premature suture fusion in Twist1 mutant mice with RNA nanoparticle gene therapy

Samuel Swearson; Steve Eliason; Dan Su; Kevin G. Rice; Brad A. Amendt

doi:10.1126/sciadv.adx9763

Back

Inhibition of craniosynostosis and premature suture fusion in Twist1 mutant mice with RNA nanoparticle gene therapy

Journal article

Open access

Peer reviewed

Inhibition of craniosynostosis and premature suture fusion in Twist1 mutant mice with RNA nanoparticle gene therapy

Samuel Swearson, Steve Eliason, Dan Su, Kevin G. Rice and Brad A. Amendt

Science advances, Vol.11(34), eadx9763

08/22/2025

DOI: 10.1126/sciadv.adx9763

PMCID: PMC12372882

PMID: 40845104

Files and links (1)

url

https://doi.org/10.1126/sciadv.adx9763View

Published (Version of record) Open Access

Abstract

Craniosynostosis is a common birth defect affecting 1 of the 2200 live births causing severe skull and cognitive defects, due to premature cranial suture fusion. The current surgical treatments require invasive calvaria vault remodeling and cranial bone resection in the baby. We demonstrate that inhibition of miR-200a in PMIS–miR-200a mice results in coronal suture fusion (craniosynostosis). Therefore, we use overexpression of miR-200a to prevent suture fusion in Twist1 mutant mice, a well-known model for craniosynostosis. We developed a PEGylated-peptide nanoparticle system to deliver plasmid DNA expressing miR-200a directly to the sutures of postnatal day 4 (P4) Twist1 mutant mice before suture fusion. Injection of the miR-200a nanoparticles under the scalp before suture fusion at P7 to P10 inhibited suture fusion. Treatments increased Gli1- and Six2-positive suture stem cells and the thickness of the periosteum layer. The treated Twist1 +/− mice increased body weight and were alert and active. We demonstrate an effective noninvasive gene therapy treatment for craniosynostosis. A therapeutic approach to inhibit premature suture fusion in craniosynostosis without invasive surgeries can improve child health.

Biomedicine and Life Sciences

Diseases and Disorders

Regeneration

SciAdv r-articles

Details

Title: Subtitle: Inhibition of craniosynostosis and premature suture fusion in Twist1 mutant mice with RNA nanoparticle gene therapy
Creators: Samuel Swearson - University of Iowa
Steve Eliason - University of Iowa
Dan Su - Stanford University
Kevin G. Rice - University of Iowa
Brad A. Amendt - University of Iowa
Resource Type: Journal article
Publication Details: Science advances, Vol.11(34), eadx9763
DOI: 10.1126/sciadv.adx9763
PMID: 40845104
PMCID: PMC12372882
NLM abbreviation: Sci Adv
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Grant note: ; RO1DE028527 / ;
Alternative title: Therapeutic treatment of craniosynostosis
Language: English
Date published: 08/22/2025
Academic Unit: Orthodontics; Anatomy and Cell Biology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Medicinal and Natural Products Chemistry
Record Identifier: 9984949233302771

Metrics

15 Record Views