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Updated: May 6, 2026
Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
Published on: June 10, 2022
Innovative Dual mRNA-Lipid Nanoparticle Therapy Targeting CRHBP and CFHR3 for Enhanced Treatment of Hepatocellular
Tianmei Fu1, Boxuan Zhou2, Yingliang Li2
1Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China.
Purpose:
Hepatocellular carcinoma (HCC) is a deadly disease requiring the identification of new therapeutic targets and strategies.
Methods:
This study identified genes linked to HCC progression via differential analysis. Key genes were identified through univariate and multivariate Cox regression analysis. The biological effects of co-expressed CRHBP and CFHR3 were evaluated in vitro. mRNAs encoding CRHBP and CFHR3 were encapsulated in lipid nanoparticles (LNPs), with the addition of SP94 peptide on the LNPs surface to enhance targeting. The therapeutic efficacy of dual-mRNA LNPs was evaluated in HCC cells and mouse models.
Results:
CRHBP and CFHR3 were closely associated with HCC progression. Low expression of CRHBP (P < 0.01, HR = 1.931 [1.174-3.175]) and CFHR3 (P < 0.05, HR = 1.755 [1.066-2.890]) was identified as a poor prognostic factor for HCC. The risk score model combining CRHBP and CFHR3 demonstrated superior predictive power (P < 0.001, HR = 2.935 [1.768-4.872]). Co-expression of CRHBP and CFHR3 significantly inhibited the malignant biological functions of HCC cells. Treatment with SP94 peptide-modified dual-mRNA LNPs markedly suppressed HCC tumor growth and exhibited excellent biocompatibility and safety.
Conclusion:
Our study proposes a dual-targeted therapeutic strategy for HCC, which may represent a promising treatment approach.
Insights
This study identified CRHBP and CFHR3 as key genes linked to hepatocellular carcinoma (HCC) progression. A novel dual-mRNA nanoparticle therapy targeting these genes showed significant efficacy in suppressing HCC tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge, necessitating novel therapeutic targets and strategies for effective treatment.
- Identifying molecular markers associated with HCC progression is crucial for developing targeted therapies.
Purpose of the Study:
- To identify novel genes implicated in hepatocellular carcinoma (HCC) progression.
- To evaluate the therapeutic potential of a dual-messenger RNA (mRNA) lipid nanoparticle (LNP) delivery system targeting specific HCC-associated genes.
Main Methods:
- Differential gene expression analysis and Cox regression identified key genes (CRHBP and CFHR3) associated with HCC.
- In vitro studies assessed the biological impact of CRHBP and CFHR3 co-expression.
- SP94 peptide-conjugated dual-mRNA LNPs were developed for targeted delivery.
- Therapeutic efficacy was evaluated in HCC cell lines and mouse models.
Main Results:
- Low expression of CRHBP and CFHR3 correlated with poor HCC prognosis.
- A risk score model incorporating CRHBP and CFHR3 demonstrated strong predictive capability for HCC.
- Co-expression of CRHBP and CFHR3 suppressed malignant cellular functions.
- Targeted dual-mRNA LNP therapy significantly inhibited HCC tumor growth with good safety.
Conclusions:
- CRHBP and CFHR3 are significant prognostic factors and potential therapeutic targets for HCC.
- Dual-mRNA LNPs, enhanced with SP94 peptide, offer a promising targeted therapeutic strategy for HCC.
- This approach demonstrates potential for improved HCC treatment outcomes.
