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Series GSE243992 Query DataSets for GSE243992
Status Public on Aug 16, 2024
Title Circular RNA vectors encapsulated in lipid nanoparticles for sustained protein replacement therapy in the retina
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Circular RNAs (circRNAs) have recently emerged as promising vectors for sustained therapeutic protein production due to their enhanced stability from exonuclease degradation. Here, we engineered circRNAs expressing reporters and neurotrophic factors, and systematically compared their expression kinetics to conventional linear mRNAs. CircRNAs achieved 10-20 fold higher and more persistent protein expression in vitro over several weeks. We further demonstrated that circRNA-expressed nerve growth factor (NGF) provided lasting neuroprotection in a neuronal injury model compared to short-lived effects from NGF protein delivery. A major challenge for clinical translation of circRNAs is efficient intracellular delivery. We address this issue through lipid nanoparticle (LNP) encapsulation technology. LNPs successfully delivered circRNAs to retina after intravitreal or subretinal injection in mice, achieving localized and prolonged expression. As proof-of-concept, LNP-formulated circRNA expressing NGF promoted retinal ganglion cell survival in a mouse optic nerve crush injury model, demonstrating advantages over NGF protein injections. Collectively, this work establishes circRNA vectors as promising candidates for safe, sustained therapeutic protein production, and elucidates a delivery platform to overcome translational barriers. Realization of this technology may enable transformative treatments for chronic neurodegenerative protein deficiency diseases.
 
Overall design Single cells from six independent mouse retina samples were captured in ?batches (CTR1,CTR2, ONC1, ONC2, ONC_NGF1, ONC_NGF2) using the 10X Chromium system.
 
Contributor(s) Xie Z, Wu C, Jiang W, Yang J
Citation(s) 39045516
BioProject PRJNA1020105
Submission date Sep 25, 2023
Last update date Aug 17, 2024
Contact name Cheng Wu
E-mail(s) wuch55@mail2.sysu.edu.cn
Phone 18846145680
Organization name Sun Yat-sen University
Street address No. 74, Zhongshan 2nd Road, Yuexiu District, Guangzhou
City Guangzhou
ZIP/Postal code 510600
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7802906 CTR1,scRNAseq
GSM7802907 CTR2,scRNAseq
GSM7802908 ONC1,scRNAseq

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Supplementary file Size Download File type/resource
GSE243992_RAW.tar 1.1 Gb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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